Apoptosis driven infection

Professional phagocytes like polymorphonuclear neutrophil granulocytes (PMN) and macrophages (MF) kill pathogens as the first line of defense. These cells possess numerous effector mechanisms to eliminate a threat at first contact. However, several microorganisms still manage to evade phagocytic killing, survive and retain infectivity. Some pathogens have developed strategies to silently infect their preferred host phagocytes. The best example of an immune silencing phagocytosis process is the uptake of apoptotic cells. Immune responses are suppressed by the recognition of phosphatidylserine (PS) on the outer leaflet of their plasma membrane. Taking Leishmania major as a prototypic intracellular pathogen, we showed that these organisms can use the apoptotic "eat me" signal PS to silently enter PMN. PS-positive and apoptotic parasites, in an altruistic way, enable the intracellular survival of the viable parasites. Subsequently these pathogens again use PS exposition, now on infected PMN, to silently invade their definitive host cells, the MF. In this review, we will focus on L. major evasion strategies and discuss other pathogens and their use of the apoptotic "eat me" signal PS to establish infection.     

An audit to evaluate the accessibility,cost, impact on work place absence and convenience of attending genitourinary medicine clinics in London and Plymouth

We conducted a survey to assess the accessibility, cost, impact on work place absence and convenience of attending two genitourinary medicine (GUM) clinics, one in London and one in Plymouth. Nine hundred and fifty-eight questionnaires were collected for analysis (448 from London [L] and 510 from Plymouth [P]). The majority in London used public transport whereas the majority in Plymouth used private transport. Journey costs were less than 5 for the majority (75% L and 59% P). Of those in employment 229/678 (44%) had to take time off from work to attend. Women were significantly less likely (13/308, 4%, 95% confidence interval (CI) 2-6.5%) than men (51/370, 14% 95% [CI] 10.317.3%) to give up annual leave to attend. Both clinics were judged accessible, affordable and convenient by the majority of clinic users.     

A case of bulimia successfully treated by cue exposure

In the present case-study, a 22-year-old female patient with a 7-year history of bulimia nervosa was treated by cue-exposure. During cue-exposure sessions the relationship between CS (stimuli associated with binge-eating behaviour) and UCS (the sensations related to the intake of binge food) was broken. As predicted, the patients' craving for food decline within as well as between cue exposure sessions and a radical decrease in the frequency of binge-eating persisted for at least nine months. Although during the therapy no explicit attention was paid to the patient's low mood and irrational self-talk, mood was improved and beliefs were less irrational after cue-exposure and at the follow-ups. The data suggest that cue exposure may be an effective part of the treatment of bulimia nervosa.     

Size-dependent effect of IgA on the IgA Fc receptor (CD89)

The IgA Fc receptor (FcR; CD89) is expressed on several types of cells of the myeloid cell lineage. We investigated whether different sizes of heat-aggregated IgA (aIgA) bind to CD89 and subsequently induce cellular activation. As a model we used the murine B cell line IIA1.6 transfected with CD89 or IIA1.6 cells transfected with CD89 as well as with the FcR γ chain to study the binding of IgA to CD89. When these cells expressing CD89 were incubated with monomeric IgA, no significant binding of IgA to the cells was detectable by fluorescence-activated cell sorter analysis; however, incubation of the cells with aggregated IgA resulted in 93 ± 2% positive cells. Incubation of the cells with different sizes of IgA-containing aggregates revealed optimal binding with aggregates containing five to six molecules of IgA per aggregate. No difference was observed between the binding to CD89 of both IgA1- or IgA2-containing aggregates. Furthermore, the binding of aIgA was found to be CD89-specific, since the binding of IgA was completely inhibited by the CD89-specific monoclonal antibody My43 and no detectable binding occurred to the IIA1.6 parent cell line. Activation studies using interleukin-2 (IL-2) production as a marker, showed that the FcR γ chain is necessary to induce cellular activation. Only cells transfected with both CD89 and the FcR γ chain (CD89⁺/γ⁺) enhance the IL-2 production 10–12-fold upon stimulation with aggregates of IgA. Furthermore, triggering of CD89 only results in increase of intracellular calcium concentration ([Ca²⁺]_i) in cells co-expressing FcR γ chain. Mutation of the tyrosine residues in the FcR γ chain immunoreceptor tyrosine-based activation motif of the FcR γ chain abolishes this increase in [Ca²⁺]_i, indicating association and involvement of the FcR γ chain in CD89-mediated signaling.     

Pericarditis and acquired immunodeficiency syndrome

In order to evaluate the frequency and clinical features of pericarditis caused by the HIV virus, 17 patients (mean age 28 years) presenting with pericarditis were investigated at the University Clinics of Mont-Amba (Za?re), between January, 1985 and December, 1986. The clinical diagnosis of AIDS had been made on the basis of the WHO criteria. An ELISA test, a tuberculin test and a T4-lymphocyte count were performed in all patients. Cardiovascular explorations were limited to electrocardiography, radiography of the chest, echocardiography and pericardial needle aspiration. HIV pericarditis accounted for 50 p. 100 of all cases of pericarditis. It was either dry or effusive with little fluid, and its clinical signs at the early stage of AIDS were retrosternal pain and pericardial friction rub. A search for anti-HIV antibodies may be negative at that stage. Diagnostic errors can be avoided if the tuberculin test is negative and if an ELISA test is performed repeatedly at 3 weeks' intervals. Pericarditis should be counted among the minor signs of AIDS.     

Checkpointinhibitoren in der Tumortherapie

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Mit der Entwicklung von Checkpointinhibitoren gelang in den letzten Jahren ein Durchbruch in der Tumortherapie....     

Comparative analysis of infection and transformation of lymphocytes from African buffalo and Boran cattle with Theileria parva subsp. parva and T. parva subsp. lawrencei.

This study compared infection and transformation of peripheral blood mononuclear cells (PBM) of Boran cattle and African buffalo in vitro to determine whether differences occurred which could account for the greater susceptibility of Boran cattle to infection with Theileria parva subsp. parva and T. parva subsp. lawrencei. PBM from buffalo and cattle had a similar percentage of cells which bound T. parva subsp. parva sporozoites (24 to 34%) and in which schizonts developed during the first week after infection (18 to 23%). Using a limiting dilution culture system, it was established, however, that a significantly higher proportion of cattle PBM transformed into continuously replicating cell lines after infection with T. parva subsp. parva than did buffalo PBM. The evidence suggests that the low capacity of T. parva subsp. parva to establish infections in buffalo compared with cattle is related to the lower frequency of buffalo cells which undergo transformation. With T. parva subsp. lawrencei, however, the frequency of transformation of buffalo PBM was higher than that for cattle PBM. The frequency of cells transformed by T. parva subsp. lawrencei, therefore, cannot account for the greater resistance of buffalo to infections with T. parva subsp. lawrencei. Buffalo must have other mechanisms, either innate or acquired, which control infection with T. parva subsp. lawrencei more efficiently than in cattle.     

Leishmania promastigotes release a granulocyte chemotactic factor and induce interleukin-8 release but inhibit gamma interferon-inducible protein 10 production by neutrophil granulocytes

Recent data from our laboratory suggest that neutrophil granulocytes (polymorphonuclear leukocytes [PMN]) can serve as host cells for Leishmania major in the early phase of infection. In line with these findings, an early influx of PMN to the infected tissues was shown by others to be associated with susceptibility to infection with L. major. The mechanisms underlying the initial PMN recruitment to the site of infection is poorly understood. In the present study we investigated whether Leishmania can influence PMN migration. Supernatants of Leishmania promastigotes were tested for their chemotactic activity using an in vitro chemotaxis assay. All Leishmania species tested (L. major, L. aethiopica, and L. donovani) displayed a marked chemotactic effect on human PMN. However, no effect on the migration of macrophages and NK cells was observed. Checkerboard analysis revealed that the observed PMN migration was due to chemotaxis rather than chemokinesis. Most of the chemotactic activity was found in fractions containing molecules with sizes between 10 and 50 kDa. Pretreatment of PMN with N-formyl-methionyl-leucyl-phenylalanine blocked the chemotactic activity of Leishmania supernatants up to 75%. In addition, we found that leishmanial contact induced the release of interleukin-8 (IL-8) and inhibited the production of gamma interferon-inducible protein 10 (IP-10) by PMN. These data suggest that infection with Leishmania promastigotes leads to PMN accumulation via the production of a chemotactic factor by the parasites, and this effect is amplified by the induction of IL-8 production in PMN. On the other hand, the inhibition of IP-10 production can lead to prevention of NK cell activation.