Susceptibility of severe combined immuno-deficient (SCID) mice to Trypanosoma brucei gambiense and T. b. rhodesiense

Susceptibility of severe combined immunodeficient (SCID) mice to 7 isolates of Trypanosoma brucei gambiense and 2 isolates of T. b. rhodesiense was examined in terms of their infectivity, course of parasitaemia, packed cell volume (PCV) and survival period in comparison with that of normal immunocompetent (BALB/c) mice. All isolates of T. b. gambiense and T. b. rhodesiense caused high (> 1 × 10⁸ parasites/ml) parasitaemia in the SCID mice, the survival periods ranged from 5 to 47 days. On the other hand, 5 of 7 isolates of T. b. gambiense developed chronic infection in the BALB/c mice with sporadic but persistent parasitaemia with less than 5 × 10⁶ parasites/ml. All the mice tested in this group survived more than 60 days after infection. In contrast, the 2 remaining isolates of T. b. gambiense and both isolates of T. b. rhodesiense showed high virulence in the BALB/c mice and killed all of them within 30 days after infection. The results demonstrate that the SCID mice, in which functional B- and T-cell-mediated immunities are congenitally lacking, are highly susceptible for 'low-virulence' T. b. gambiense . This makes SCID mice useful tools for the isolation of parasites from T. b. gambiense sleeping sickness patients and the propagation of large amounts of such parasites.     

Interferon-gamma and the induction of protective lgG2a antibodies in non-lethal Plasmodium berghei infections of mice

Mice treated with anti-IFN-gamma monoclonal antibodies were unable to recover from infection with an attenuated variant of P. berghei (Pb XAT) which causes non-lethal malaria in normal mice. On the other hand, treatment with anti-lL-4 monoclonal antibodies had no effect on the course of infection. IFN-gamma was produced by spleen cells in vitro during the early phase of the infection. Treatment with anti-IFN-gamma suppressed development of an anti-plasmodial IgG2a immunoglobulin isotype in the serum of infected mice whereas anti-IL-4 interfered with the IgGl response. An lgG2a fraction of immune serum collected from mice that had recovered from Pb XA T transferred immunity to naive mice but the IgGl fraction did not. When glutaraldehyde fixed parasitized erythrocytes were incubated with immune serum in suspension, specific IgG2a antibodies were detected by fluorescein staining on the membranes of cells infected with mature stages of parasites. These results indicate that IFN-gamma is a key to inducing B cells to produce the protective anti-plasmodial IgG2a immunoglobulin isotype. Antibody-dependent cell-mediated parasite killing seems to be involved in the mechanism of recovery from infection with Pb XAT.     

Regulation of parasite-specific antibody responses in resistant (C57BL/6) and susceptible (C3H/HE) mice infected with Trypanosoma (trypanozoon) brucei brucei

After infection with 10(3) T. brucei GUTat 3.1, C57BL/6 mice produced antibody responses and controlled the first parasitaemic wave whereas C3H/He mice did not. The inability of C3H/He mice to control parasitaemia resulted from an impaired ability of parasite-induced antibody-containing cells to secrete immunoglobulin. Antibody-containing cells in infected C3H/He mice regained the ability to secrete antibody within 24 h after trypanosome elimination by treatment with Berenil, suggesting that the block in antibody secretion was maintained by living parasites or short-lived components of degenerating parasites. Infected C3H/He mice also had an impaired ability to produce a rabbit erythrocyte-specific antibody response on challenge with rabbit erythrocytes and this response recovered when parasites were eliminated from the blood 24 h before analysis. It was not possible to inhibit secretion of antibody by rabbit erythrocyte-induced plasma cells either by incubating them with serum from infected C3H/He mice or by injecting large numbers of living trypanosomes into C3H/He mice already responding to rabbit erythrocytes. The process leading to failure of parasite and rabbit erythrocyte-induced antibody-containing cells to become high rate antibody-secreting cells was not identified but did not appear to correlate with any obvious change in the intra-cellular morphology of the antibody-containing cells.     

Protective immune response to Plasmodium chabaudi, developed by mice after drug controlled infection or vaccination with parasite extracts: analysis of stage specific antigens from the asexual blood cycle

Summary The protective immune response to asexual blood infection by Plasmodium chabaudi was studied in mice immunized either by drug controlled infection or by vaccination with preparations of merozoïtes or free parasites at different stages of development. Animals immunized by the first method developed a sterile immunity. The passive transfer of their serum protected naive recipients from the lethal development of the infection, but affected only moderately the initial course of the parastiaemia. Animals immunized with either ring, schizont or merozoi'te preparations exhibited a limited but significant resistance to infection: when challenged with 10⁶ parasites of the homologous strain they exhibited a reduced parasitaemia as compared to control mice, and in addition, 50% of them recovered from the infection. Immunochemical analysis of parasite antigens showed that a family of high molecular weight proteins synthesized essentially at the schizont stage and conserved in the merozoites are important immunogens. Quantitative rather than qualitative differences were observed in the pattern of parasite proteins immunoprecipitated by serum of animals exhibiting sterile immunity or moderate protective immunity. A schizont specific polypeptide of mol. wt 82 Kd which is found in the surface of the merozoite is preferentially immunoprecipited by serum from animals exhibiting sterile immunity.     

Evidence for determining parasitic factors in addition to host genetics and immune status in the outcome of murine Leishmania infantum visceral leishmaniasis

C.B-17 SCID and congenic BALB/C mice were used to examine Leishmania infantum strain pathogenicity independently of host genetic factors. While parasite loads were significantly higher in immunodeficient mice than in immunocompetent mice, the kinetics of infection during a long-term follow-up were similar, suggesting that intrinsic parasitic factors also influence the outcome of L. infantum infection.     

Parasite-specific IgM plays a significant role in the protective immune response to asexual erythrocytic stage Plasmodium chabaudi AS infection

A comparison of Plasmodium chabaudi AS infection in BALB/c and BALB/c IgM-deficient mice demonstrated a protective role for IgM during infection. IgM^−/– mice, unlike µMT mice, display competent B cell humoral immune responses. Increased susceptibility of IgM^−/– mice was demonstrated by increased mortality, an advanced ascending infection and higher peak parasitaemia, as well as enhanced anaemia and weight loss compared with wild-type mice. The recrudescent parasitaemias were also higher in the IgM^−/– mice. Early specific IgM production in P. chabaudi-infected wild-type mice was followed by IgG1 and IgG2a production, while IgG1 and IgG2a production in IgM^−/– mice was preceded by specific IgD production. No protective role for natural IgM against P. chabaudi AS infection was detected as passive transfer of naïve WT serum into IgM^−/– mice did not alter the disease outcome or reduce parasite numbers. Passive transfer of WT antiserum, containing predominantly specific IgM, into IgM^−/– mice delayed the ascending parasitaemia and reduced mortality. Similarly, coating parasitized red blood cells with WT antiserum, but not IgM^−/– antisera, prior to infection also slightly delayed the ascending acute parasitaemia. Specific IgM therefore plays an important role in the limitation of parasite replication during asexual erythrocytic P. chabaudi AS infection.     

Reduced Plasmodium berghei sporozoite liver load associates with low protective efficacy after intradermal immunization

Studies in animal models suggest that protection against malaria induced by intradermal (ID) administration of sporozoites is less effective compared to intravenous injection (IV). We investigated in a murine model the protective efficacy and immune responses after ID or IV immunization of sporozoites. Mice were immunized via either IV or ID route with Plasmodium berghei sporozoites in combination with chloroquine treatment (CPS) (allowing full liver stage development) or by γ‐radiation‐attenuated sporozoites (RAS) (early liver stage arrest). While IV immunization with both RAS and CPS generated 90–100% protection, ID immunization resulted in reduced levels of protection with either immunization strategy in both Balb/cByJ (50%) and C57BL/6j mice (7–13%). Lower protection by ID routing associated with a 30‐fold lower parasite liver load [P < 0.001 (χ² = 49.08, d.f. = 1)] assessed by real‐time in vivo imaging of bioluminescent P. berghei parasites. Unlike IV, ID immunization did not result in expansion of CD8+ T cells with effector memory phenotype and showed lower IFNγ responses irrespective of the immunization regime. In conclusion, protection against sporozoite infection is likely dependent on parasite liver infection and subsequently generated cellular immune responses.     

Role of mononuclear phagocytes in elimination of Plasmodium chabaudi AS infection

Summary The role of mononuclear phagocytes in acquired immunity resulting in the intraerythrocytic destruction and elimination of malarial parasites was investigated in the murine model of infection with Plasmodium chabaudi AS. Mice were treated 1 day before or 6 days after infection with agents which either result in augmentation or activation of the non–specific, microbicidal effector function of mononuclear phagocytes or in depletion of cells of this lineage. To examine the effect of agents which activate mononuclear phagocytes, A/J mice, which are susceptible to P. chabaudi AS and exhibit fulminant parasitaemia and death within 10 days of intraperitoneal infection with 10⁶ P–RBC, were treated intravenously with muramyl dipeptide (MDP) or liposome–encapsulated MDP–glycerol dipalmitate (MDP–GDP). Treatment administered 1 day before infection was ineffective. Treatment on day 6 post–infection with liposome–encapsulated MDP–GDP (1 ftg) resulted in a significant decrease in parasitaemia on day 8 and survival, while treatment with free MDP (100 ^g) resulted only in a significant decrease in parasitaemia. To examine the effect of depletion of mononuclear phagocytes, C57BL/6 mice, which are resistant to P. chabaudi AS infection and eliminate the parasite by 4 weeks, were treated intravenously with 3 mg silica. Silica administered 1 day before or 6 days post–infection abrogated resistance resulting in a delay in elimination of the parasite and host mortality. Treatment on day 6 was more effective, with death by day 13 post–infection of 70% of the normally resistant C57BL/6 mice which exhibited fulminant parasitaemia levels. These results thus provide in–vivo evidence that mononuclear phagocytes play a critical role in the elimination of infection with the murine malaria species P. chabaudi AS. Furthermore, these results suggest that the time of administration of agents which alter mononuclear phagocyte function may be important in determining their effect on host antimalarial defences.     

Regulation of the growth and differentiation of Trypanosoma (Trypanozoon) brucei brucei in resistant (C57B1/6) and susceptible (C3H/He) mice

While Trypanosoma brucei brucei GUTat 3 were equally infective for C3H/He and for C57Bl/6 mice at doses ranging from 5 to 5 x 10(3) organisms and had similar prepatent periods in both strains of mice, infected C57Bl/6 mice displayed lower parasitaemia, shorter times to parasite wave remission and survived for a longer time than infected C3H/He mice. Parasite growth and differentiation rates and host immune responses were similar for the first 5 days in both strains of mice after infection with 10(3) T.b.brucei GUTat 3 but, thereafter, parasite differentiation proceeded more rapidly and specific antibodies reached higher titres in C57Bl/6 than in C3H/He mice. In contrast, parasite growth and differentiation rates were similar in irradiated mice of both strains. Furthermore, following inoculation of intact mice with irradiated T.b.brucei GUTat 3, C3H/He mice actually mounted higher titred antibody responses than C57Bl/6 mice showing that they were not intrinsically defective in their capacity to respond to GUTat 3 antigens. Parasite differentiation occurred at the same rate in irradiated (650r) C57Bl/6 mice and in irradiated C57Bl/6 mice reconstituted with syngeneic spleen cells although T.b.brucei GUTat 3 specific antibody was detected in the latter mice prior to peak parasitaemia. Furthermore, it was shown directly in C57Bl/6 mice that there was no selective destruction of slender form T.b.brucei GUTat 3 parasites during the phase of accumulation of stumpy form parasites. These studies indicate that the more rapid differentiation of T.b.brucei GUTat 3 parasites in infected C57Bl/6 mice as compared to infected C3H/He mice was unlikely to be directly related to the more efficient antibody response in the infected C57Bl/6 mice. The observations suggest that there might be an association between host mechanisms which regulate differentiation of T.b.brucei parasites and those which regulate antibody responses.     

Systemic lymphocyte activation modulates the severity of diet-induced acute pancreatitis in mice.

To examine the role of lymphocyte activation in the development of local and systemic complications in acute pancreatitis, we compared disease severity of choline-deficient, 0.5% ethionine supplemented (CDE) diet-induced acute pancreatitis in T- and B-cell deficient SCID mice and immunocompetent C.B-17 mice. Twenty-five female SCID and 17 female C.B-17 mice were fasted for 24 h and fed a CDE diet for 72 h. Twenty SCID and 12 C.B-17 mice were bled and their organs removed for histologic evaluation. Five control animals of both kinds were fed a regular diet for 6 days. Lung, kidney, and pancreas were examined microscopically, and pancreatic damage scored. Apoptosis was detected by DNA nick-end labeling and confirmed by DNA laddering. Trypsinogen-activation peptide was measured by enzyme-linked immunosorbent assay (ELISA), and the catalytic activity of PLA2 was determined by a radiometric assay. Four-day mortality was 10% in SCID and 33% in C.B-17 mice, and 10-day mortality was 0 in SCID and 60% in C.B-17 mice. SCID mice had mild pulmonary damage, whereas pulmonary injury was severe in C.B-17 mice. Pancreatic damage was severe in both groups. Even though in situ staining of apoptotic cells was found in all pancreatitis animals, apoptosis was confirmed by DNA laddering only in C.B-17 mice. In SCID mice, apoptotic cell staining positively correlated with necrosis (r = 0.91; p < 0.001). Plasma TAP and PLA2 catalytic activity did not differ significantly between the groups. In conclusion, the absence of T and B lymphocytes prevents severe pulmonary injury resulting from acute pancreatitis but does not influence pancreatic or renal damage. Our results suggest that systemic lymphocyte activation does not affect the initiating events that trigger pancreatic injury but modulates the systemic response, in particular, pulmonary injury caused by acute pancreatitis.     

Early treatment during a primary malaria infection modifies the development of cross immunity

We have used a murine model to study the kinetics of cross-protection when a primary infection is halted at different times. We analysed how parasitaemia is modified during a second infection with the homologous parasite, a heterologous parasite, or a mixture of the two. In addition, possible mechanisms involved in cross-protection were analysed. Results show that treatment with pyrimethamine on day 5 during a primary infection with P. chabaudi AS (non-lethal), prevents the generation of cross-protection to a new challenge with lethal P. yoelii 17XL. In contrast, when treatment is on day 7, mice survive a P. yoelii infection. Differences between both groups suggest that in order for 'preimmune' mice to survive a lethal challenge, a predominantly TH2-type response is required, with a higher mRNA expression level of IL-4 and IL-10, and a lower mRNA expression of IFN-gamma. This work shows that an early treatment of a malaria infection produced by a non-lethal parasite drives the immune response towards a loss of cross-protection to further infections, in particular with more virulent parasites. This finding should be taken into account for the development of effective malaria vaccines.     

Endogenous galectin-3 controls experimental malaria in a species-specific manner

Galectins are evolutionarily conserved glycan-binding proteins with pleiotropic roles in innate and adaptive immune responses. Galectin-3 has been implicated in several immunological processes as well as in pathogen recognition through specific binding to glycosylated receptors on the surface of host cells or microorganisms. In spite of considerable evidence supporting a role for galectin-3 in host-pathogen interactions, the relevance of this lectin in the regulation of the host defence mechanisms in vivo is poorly understood. In this study, we analysed the impact of galectin-3 deficiency during infection with three distinct species of rodent malaria parasites, Plasmodium yoelii 17XNL, Plasmodium berghei ANKA and Plasmodium chabaudi AS. We found that galectin-3 deficiency showed a marginal effect on the course of parasitaemia during P. chabaudi infection, but did not alter the course of parasitaemia during P. berghei infection. However, lack of galectin-3 significantly reduced P. yoelii parasitaemia. This reduced parasitaemia in Lgals3(-/-) mice was consistent with higher titres of anti-P. yoelii MSP1(19) IgG2b isotype antibodies when compared with their wild-type counterparts. Our results reflect the complexity and singularity of host-pathogen interactions, indicating a species-specific role of endogenous galectin-3 in the control of parasite infections and the modulation of antibody responses.     

The relative contribution of antibody production and CD8+ T cell function to immune control of Trypanosoma cruzi

The life cycle of the protozoan parasite Trypanosoma cruzi in mammalian hosts includes both non-dividing trypomastigote forms which circulate in the blood and replicating intracellular amastigotes which reside within the cytoplasm of a variety of host cells. In this study we have used mice with induced mutations in genes responsible for either antibody production or cytolytic T lymphocyte (CTL) function to examine the relative contributions of these effector mechanisms to control of T. cruzi. Mice deficient in the production of antibodies exhibited a delay in the rise in acute phase parasitaemia and an extended time to death relative to mice lacking CD8⁺ T cells. Nevertheless, B cell deficient mice eventually succumbed to the infection. Prior infection with an avirulent strain of T. cruzi failed to protect either CD8⁺ T cell-deficient mice or B cell deficient mice from challenge infection with virulent parasites. In contrast, mice with disruptions in the genes controlling perforin- or granzyme B-mediated cytolytic pathways had parasitaemia and mortality rates similar to wild-type mice and were protected from secondary infection by prior exposure to avirulent parasites. These results 1) confirm that antibody production, although secondary in importance to cellular responses, is nevertheless absolutely required and 2) perforin- or granzyme B-mediated lytic pathways are not required for control of T. cruzi infection.     

Protective immunity to malaria: studies with cloned lines of Plasmodium chabaudi and P. berghei in CBA/Ca mice. I. The effectiveness and inter-and intra-species specificity of immunity induced by infection

CBA/Ca mice were immunized by infection with cloned lines of Plasmodium berghei (isolates ANKA, KSP-11). Plasmodium chabaudi chabaudi (AS, CB) or Plasmodium chabaudi adami (DS) and then challenged with either homologous or heterologous parasites. Protective responses were assessed in immune mice relative to the controls by their ability to (i) extend the time taken for the mean parasitaemia to reach a predetermined level (1% or 0.1%) (ii) reduce peak parasitaemia (iii) resolve the parasitaemia sooner and/or (iv) control or eliminate recrudescences. At both the inter- and intra-species level, immunity appeared largely specific for the cloned line inducing it. At the interspecies level marginally effective cross-immunity was sometimes evident, thus P. berghei KSP-11 immune mice displayed some immunity against P.c. chabaudi AS, although immunity to this parasite was relatively ineffective against P. berghei ANKA or KSP-11. Cross-immunity was more apparent between the subspecies P.c. adami and P.c. chabaudi and between cloned lines of the latter parasite derived from the AS and CB isolates. These data reflect considerable inter- and intra-species structural and immunogenic differences in certain antigens of parasitized erythrocytes and merozoites, which have been identified in a number of murine malarias and associated with protective immunity. Similar differences recently identified in the equivalent antigens of the human parasite P. falciparum may therefore have important implications for protective immunity in man.     

Interleukin 1 participates in the development of anti-Listeria responses in normal and SCID mice.

Using T- and B-cell deficient C.B-17 mice with the scid mutation, we have previously documented the existence of a T-cell-independent but interferon gamma-dependent pathway of macrophage activation that confers upon the host partial resistance to the facultative intracellular bacterium Listeria monocytogenes. This pathway is operative in both normal and SCID mice and consists of at least four components: interferon gamma, tumor necrosis factor, macrophages, and natural killer cells. Here we demonstrate that interleukin 1 also participates in this pathway but at a different site of action. Using monoclonal antibodies that neutralize the biologic activities of interleukin 1 alpha and interleukin 1 beta, we document that interleukin 1 participates neither directly in the induction of interferon gamma from isolated SCID natural killer cells nor in the antigen-specific activation of CD4+ T cells derived from Listeria-immune C.B-17 mice. In contrast, injection of a mixture of anti-interleukin 1 alpha, anti-interleukin 1 beta, and a newly derived monoclonal antibody specific for the murine type I interleukin-1 receptor into either SCID or normal C.B-17 mice blocked the in vivo elaboration of class II major histocompatibility complex-positive macrophages after infection of the animals with Listeria. Moreover, SCID mice treated with the anti-interleukin-1 mixture failed to control the growth of Listeria in vivo and eventually succumbed to the infection. These results document that endogenously produced interleukin 1 plays an obligate role in the Listeria-dependent induction of activated macrophages in vivo and demonstrate that the action of interleukin 1 is distinct from the generation of natural killer cell-derived interferon gamma.     

Antecedent Nippostrongylus infection alters the lung immune response to Plasmodium berghei

In endemic regions, it is not uncommon for patients to be co‐infected with soil‐transmitted helminths and malaria. Although both malaria and many helminth species use the lungs as a site of development, little attention has been paid to the impact that pulmonary immunity induced by one parasite has on the lung response to the other. To model the consequences of a prior hookworm exposure on the development of immunity to malaria in the lungs, mice were infected with Nippostrongylus brasiliensis and 2 weeks later challenged with Plasmodium berghei. We found that a pre‐existing hookworm‐induced type 2 immune environment had a measurable but modest impact on the nature of the malaria‐driven type 1 cytokine response in the lungs that was associated with a transient effect on parasite development and no significant changes in morbidity and mortality after malaria infection. However, prior hookworm infection did have a lasting effect on lung macrophages, where the malaria‐induced M1‐like response was blunted by previous M2 polarization. These results demonstrate that, although helminth parasites confer robust changes to the immunological status of the pulmonary microenvironment, lung immunity is plastic and capable of rapidly adapting to consecutive heterologous infections.     

约氏疟原虫某些生物学特性的实验研究

本文报告了约氏疟原虫(Plasmodium yoelii By 265 strain)有以下的生物学特性:1.血传和蚊传的小鼠分别于24～96h和2～8d首次查到原虫,见虫后的原虫血症和配子体血症,在消长过程中分别可见2～4和2～3个峰;2.无论接种虫血或子孢子.蚊媒感染高峰均出现于首次见虫的第3d或第4d;以蚊胃感染率为指标,未见配子体活力有明显的周期性,而感染度则显示上升期、高峰期和下降期三个不同时期;3.蚊媒感染高峰一般较接种子孢子时间晚7～8h;4.见虫后第10d,已“失活”的配子体经血传给健康小鼠12h后,可使90％的蚊媒获得感染,且卵囊指数高达63.6;5.在保种过程中,最佳血传时间为种源鼠见虫的第6～8d,至第25代,配子体对蚊媒仍有较强的感染力。     

Adoptive transfer of immunity with intraepithelial lymphocytes in Cryptosporidium parvum-infected severe combined immunodeficient mice

BACKGROUND: Intestinal infections with the protozoan parasite Cryptosporidium parvum are prevalent in both immunocompetent and immunocompromised hosts. Although C parvum is an important cause of outbreaks and opportunistic infections worldwide, little is known about protective mucosal immune responses. This is in part because animal models of infection are limited to those with genetic or induced immunodeficiencies. METHOD: In this report, we isolated immune (primed) or nonimmune (unprimed) intraepithelial lymphocytes (IEL) from BALB/cJ mouse intestines, adoptively transferred them into C parvum-infected severe combined immunodeficient (SCID) mice, and evaluated infection and cell phenotype responses. RESULTS: Control SCID mice that received no IEL shed large numbers of oocysts throughout the experimental period (day 18 to day 72). Transfer of primed IEL significantly reduced fecal oocyst shedding in recipient SCID mice compared with SCID mice that received unprimed IEL or no IEL. SCID mice transferred with unprimed IEL shed variable numbers of fecal oocysts that increased and decreased in bursts until day 57 after infection. SCID mice transferred with primed IEL exhibited significantly higher proportions of T-cell receptor (TCR) alphabeta+, CD8+, and CD8alphabeta+ EL compared with inoculated SCID mice that received unprimed or no IEL. CONCLUSION: We conclude that primed IEL from immunocompetent mice may influence protective mucosal response against cryptosporidiosis when transferred into SCID mice. In addition, the increased percentage of TCR alphabeta+, CD8+, CD8alphabeta+ IEL in recipient SCID mice may reflect mucosal cell populations involved in these responses during chronic C parvum infection.     

Neutrophils have a protective role during early stages of Leishmania amazonensis infection in BALB/c mice

Neutrophils are involved in the early stages of immune responses to pathogens. Here, we investigated the role of neutrophils during the establishment of Leishmania amazonensis infection in BALB/c and C57BL/6 mice. First, we showed an accumulation of neutrophils between 6 and 24 h post‐infection, followed by a reduction in neutrophil numbers after 72 h. Next, we depleted neutrophils prior to infection using RB6‐8C5 or 1A8 mAb. Neutrophil depletion led to faster lesion development, increased parasite numbers and higher arginase activity during the first week of infection in BALB/c mice, but not in C57BL/6 mice. Increased susceptibility was accompanied by augmented levels of anti‐L. amazonensis IgG and increased production of IL‐10 and IL‐17. Because IL‐10 is a mediator of susceptibility to Leishmania infection, we blocked IL‐10 signalling in neutrophil‐depleted mice using anti‐IL‐10R. Interestingly, inhibition of IL‐10 signalling abrogated the increase in parasite loads observed in neutrophil‐depleted mice, suggesting that parasite proliferation is at least partially mediated by IL‐10. Additionally, we tested the effect of IL‐17 in inflammatory macrophages and observed that IL‐17 increased arginase activity and favoured parasite growth. Taken together, our data indicate that neutrophils control parasite numbers and limit lesion development during the first week of infection in BALB/c mice.     

Parasitaemia levels in Plasmodium chabaudi infected‐mice modify IFN‐γ and IL‐10 expression after a homologous or heterologous challenge

CB6F1 mice infected with the nonlethal Plasmodium chabaudi chabaudi AS suffer parasitaemia levels up to 40% (full parasitaemia, FP) and develop both homologous and heterologous (against the lethal Plasmodium yoelii 17XL) protective immunity. However, if mice are treated with anti‐malarial drug when parasitaemia is below 10% (low parasitaemia, LP), they only develop homologous immunity. For the better understanding of this interesting dissociation related to the degree of parasitaemia, in this work, we studied the genetic expression of some cytokines. We found that during primary parasitaemia both FP and LP mice showed at first a TNF‐α, IL‐2 and IFN‐γ response which is followed by an IL‐4 and IL‐10 response. When FP and LP mice were challenged with either the homologous (FP + AS and LP + AS mice) or the heterologous parasite (FP + 17XL and LP + 17XL mice), we observed that LP + 17XL mice, which failed to develop heterologous immunity and succumbed to the challenge, showed a stronger IFN‐γ and a weaker IL‐10 expression than FP + 17XL mice, which developed heterologous immunity and survived the challenge. The importance and the possible implications of these findings are discussed.