Strain differences in susceptibility to murine respiratory mycoplasmosis in C57BL/6 and C3H/HeN mice.

Not only is murine respiratory mycoplasmosis, due to Mycoplasma pulmonis, a complication of biomedical research, it provides excellent animal models to study the development of a naturally occurring respiratory disease induced by an infectious agent. The understanding of pathogenic mechanisms of disease can be greatly facilitated by studying genetic differences in susceptibility. Five strains of mice with various H-2K haplotypes were examined for their susceptibility to murine respiratory mycoplasmosis; of these, C57BL/6 and C3H/HeN mice were chosen for additional study. There were no significant differences in the incidence of infection in either the upper or lower respiratory tract or in the severity of upper respiratory tract lesions in the two strains as determined at 14 days postinfection. In striking contrast, the C57BL/6 mice were significantly more resistant to the development of gross and microscopic lung lesions and to death due to pneumonia as shown by an almost 100-fold difference in the 50% lethal dose, 50% gross pneumonia dose, and 50% microscopic lesion dose. The most apparent differences in lung lesions between the two strains were in the severity of acute lesions of the bronchial epithelium, the amount of mixed inflammatory response in the alveoli, and the amount of lymphoid infiltrates. All were significantly more severe in C3H/HeN mice. In addition, more C3H/HeN mice developed antibody responses to M. pulmonis. The amount of antibody correlated with lesion severity in both strains.     

Immunopathological response of C57BL/6 and C3H/HeN mice to Aspergillus fumigatus antigens

C3H/HeN and C57BL/6 mice were exposed to culture filtrate (CF) and mycelial extracts (ME) of Aspergillus fumigatus (Af) intranasally. Animals received 6, 8 or 10 biweekly doses and were sacrificed 2 weeks after the last dose was administered. Specific antibodies against Af were detected in their sera by biotin-avidin-linked immunosorbent assay (BALISA). Antibodies against Af belonging to all isotypes showed an increase in both strains of mice. A progressive increase in IgG and IgA antibody isotypes against both CF and ME antigens was detected in C3H/HeN mice during the entire experimental period, whereas most antibody levels peaked after the 8th dose and remained steady or decreased slightly in the C57BL/6 strain. Lung lavage studies showed a relative decrease in the number of macrophages and an increase in the number of lymphocytes after the 6th and 8th instillation of Af antigens in both strains of mice. Histology of the lung demonstrated a progressive inflammatory reaction in C57BL/6 mice during the experimental period. On the other hand, the C3H/HeN mice showed a negligible inflammatory pulmonary reaction. The antibody responses and inflammatory changes detected in the lungs of mice exposed to Af antigens are comparable to allergic bronchopulmonary aspergillosis (ABPA) in humans and hence this model will be of value in understanding the disease mechanism in ABPA and related diseases.     

Depletion of alveolar macrophages exacerbates respiratory mycoplasmosis in mycoplasma-resistant C57BL mice but not mycoplasma-susceptible C3H mice.

Indirect evidence suggests that innate immune mechanisms involving alveolar macrophages (AMs) are of major importance in antimycoplasmal defense. We compared the effects of AM depletion on intrapulmonary killing of Mycoplasma pulmonis during the early phase of infection in mycoplasma-resistant C57BL/6NCr (C57BL) and mycoplasma-susceptible C3H/HeNCr (C3H) mice. More than 80% of AMs were depleted in both strains of mice by intratracheal insufflation of liposome-encapsulated dichloromethylene bisphosphonate (L-Cl2MBP), compared to no significant AM depletion in either strain following insufflation of liposome-encapsulated phosphate-buffered saline (L-PBS), PBS alone, or no treatment. AM-depleted (L-Cl2MBP) and control (L-PBS) mice were infected intranasally with 10(5) CFU of M. pulmonis UAB CT, and their lungs were quantitatively cultured to assess intrapulmonary killing at 0, 8, 12, and 48 h postinfection. AM depletion exacerbated the infection in C57BL mice by reducing killing of the organism to a level comparable to that in C3H mice without AM depletion. In contrast, AM depletion did not alter killing in C3H mice. These results directly identify the AM as the main effector cell in early pulmonary antimycoplasmal defense and suggest that differences in mycoplasmal killing by AMs may explain the resistance of C57BL mice and the susceptibility of C3H mice to mycoplasmal infection.     

Early local cytokine profiles in strains of mice with different outcomes from chlamydial genital tract infection

In this study, we expand on the examination of genetically determined differences in host responses that correlate with clearance of Chlamydia trachomatis from the genital tract. We infected C57BL/6, BALB/c, and C3H/HeN mice with the mouse pneumonitis agent of C. trachomatis (MoPn). C57BL/6 mice had the shortest course of infection (22 days) and the lowest incidence of severe hydrosalpinx. BALB/c mice also had a short course of infection (25 days), but all developed hydrosalpinx. C3H/HeN mice had the longest course of infection (38 days), and all developed severe hydrosalpinx. Determination of local cytokine responses by enzyme-linked immunosorbent assay (ELISA) of genital tract secretions revealed that the levels of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) were significantly increased in the C57BL/6 and BALB/c strains compared to those in the C3H/HeN strain whereas the level of IL-6 was not different. The level of the neutrophil chemokine macrophage inflammatory protein 2 (MIP-2) was increased during the first week of infection in all three strains but was significantly higher in the BALB/c strain, the strain with the most rapid influx of neutrophils into the genital tract. Prolonged detection of MIP-2 in C3H/HeN mice was associated with a protracted presence of neutrophils in the genital tract. Early increases in the levels of the proinflammatory cytokines TNF-alpha and IL-1beta are associated with earlier eradication of infection in the C57BL/6 and BALB/c strains than in the C3H/HeN strain. Increased levels of MIP-2 and neutrophils in BALB/c and C3H/HeN mice relative to C57BL/6 mice suggest that these responses may contribute to pathology.     

Severity of group B streptococcal arthritis in selected strains of laboratory mice

The susceptibilities of C3H/HeN, BALB/c, and C57BL/6N mouse strains to group B streptococci (GBS) infection were evaluated. C3H/HeN mice developed severe polyarthitis; mild lesions and no lesions were observed in BALB/c and C57BL/6N mice, respectively. A correlation between the severity of arthritis, the number of GBS in the joints, and local interleukin-6 and interleukin-1beta production was evident.     

γ射线对C57BL/6J和C3H/HeN小鼠肺成纤维细胞生物学行为影响的比较研究

目的比较C57BL/6J和C3H/HeN两种小鼠肺成纤维细胞以不同剂量的60Coγ射线照射后生物学行为的异同。方法原代分离培养C57BL/6J和C3H/HeN两种小鼠肺成纤维细胞(LF),应用2、4、6和8Gy的60Coγ射线照射后,通过MTT比色法、流式细胞术、AgNOR染色和免疫荧光细胞化学染色法,检测照射后两种LF的增殖活力、细胞周期以及a-平滑肌肌动蛋白(a-SMA)、基质金属蛋白酶-1(MMP-1)和金属蛋白酶组织抑制剂-1(TIMP-1)表达的变化。结果以2~8Gy照射后,C57BL/6J和C3H/HeN小鼠的LF增殖活力与正常对照组相比较未见明显增强。照射后,C57BL/6J小鼠的LF非整倍体增多,a-SMA高表达,MMP-1的表达呈弱阳性,TIMP-1的表达呈增强趋势。照射后,C3H/HeN小鼠的LF出现G2-M期阻滞,a-SMA的表达减弱至消失,MMP-1和TIMP-1的表达均呈增强趋势。结论以60Coγ射线照射后,C57BL/6J和C3H/HeN两种小鼠的LF生物学行为不同,C57BL/6J小鼠的LF呈“活化”状态,为该种小鼠易发生肺纤维化的细胞学基础提供了实验依据。     

Relative susceptibilities of inbred mouse strains C57BL/6 and A/J to infection with Histoplasma capsulatum.

Differences in the 30-day survival of Histoplasma capsulatum after intravenous injection indicated that the A/J strain of inbred mouse was more resistant to experimental infection than was the C57BL/6 strain. CFU from the spleens of infected animals increased during the first week after injection but gradually declined over the next 3 weeks. The CFU per gram of tissue in the C57BL/6 animals were 10- to 100-fold higher than were those in the A/J mice during the time between 7 and 28 days after infection. The units of gamma interferon (IFN-gamma) in supernatants of spleen cells stimulated with heat-killed yeast cells of H. capsulatum reached a peak at the time of the largest number of CFU per gram of tissue. The titers of IFN-gamma at days 3 to 5 were higher in the A/J mice than they were in the C57BL/6 mice, but from days 7 to 28, the titers of IFN-gamma were not correlated with the more efficient clearance of the fungus from the spleens of A/J mice. The L3T4+ spleen cells were shown to be active IFN-gamma producers. Treatment of Histoplasma-infected mice with anti-IFN-gamma antibody resulted in much larger tissue burdens of the fungus in the lungs and spleens of treated animals than in untreated animals. There was no marked difference in the result of treatment with anti-IFN-gamma antibody between A/J and C57BL/6 mice. Treatment of Histoplasma-infected mice with recombinant murine IFN-gamma did not alter the course of infection in either inbred strain of mouse.     

Difference in susceptibility to gram-negative urinary tract infection between C3H/HeJ and C3H/HeN mice

The difference in susceptibility to urinary tract infection between C3H/HeJ and C3H/HeN mice was tested for with gram-negative strains differing in lipopolysaccharide composition. Recently, impaired clearance of Escherichia coli from the kidney of C3H/HeJ compared to C3H/HeN mice was shown to be correlated with the LPS low responsiveness. In this study, a difference in clearance from the kidneys of C3H/HeJ and C3H/HeN mice was found only with lipopolysaccharide-containing bacteria. Gram-positive bacteria, e.g., Staphylococcus saprophyticus and Streptococcus agalactiae, were recovered in essentially equal numbers from the kidneys of mice of both strains. In contrast, of the lipopolysaccharide-containing strains used, all persisted in higher numbers in the kidneys of C3H/HeJ mice than in the kidneys of C3H/HeN mice. Variations in the O side chain did not eliminate this difference. E. coli Hu734 O75+K5+ and the rfb- mutant O75-K5+ remained in similar numbers in C3H/HeJ mice, although O75-K5+ was eliminated more rapidly in C3H/HeN mice. The core structure did not affect the differential persistence in the two mouse strains. The rfb mutants with R1-R4 cores were eliminated after 24 h from the C3H/HeN mice, but remained in significant numbers in the kidneys of C3H/HeJ mice. Even the Re mutant of Salmonella minnesota persisted in low numbers in C3H/HeJ mice. The relative bacterial recovery from either mouse strain was related to the overall virulence of the infecting bacterial strain, but the difference between C3H/HeJ and C3H/HeN mice was associated with responsiveness to parts of lipopolysaccharide common to the bacterial strains tested.     

Clearance of different strains of Mycoplasma pulmonis from the respiratory tract of C3H/HeN mice.

Pathogen-free C3H/HeN mice were exposed by aerosol to Mycoplasma pulmonis PG34(ASH), UAB 5782C, M1, UAB T, or UAB CT, and clearance of mycoplasmas from the nasal passages, trachea, and lungs was determined during the first 72 h postinoculation (PI). There were differences among strains of mycoplasmas in physical removal of organisms and in killing by nonspecific factors in the nasal passages and trachea. The avirulent strain, PG34(ASH), was quickly removed from the nasal passages and trachea. Physical removal of the other mycoplasmal strains occurred slowly, with 60 to 89% of the radioactive label remaining in the nasal passages and trachea even after 72 h. There were significant differences in killing among mycoplasmal strains by nonspecific host mechanisms in the nasal passages, trachea, and lungs. Strain UAB T was quickly killed at all levels of the respiratory tract. Strains UAB 5782C and M1 were killed at all three sites by 2 to 4 h PI. The most virulent strain, UAB CT, was killed much more slowly than the other strains. However, there was no statistical difference in the relative numbers of mycoplasmas present in the lungs at 72 h PI among strains UAB CT, UAB 5782C, and M1. These studies showed that the different mycoplasmal strains were cleared from the respiratory tract by different mechanisms and suggest that the differences in virulence among the mycoplasma strains can be explained, in part, by the differences in elimination of the organisms from the respiratory tract by nonspecific host defense mechanisms.     

Experimental Cryptosporidium parvum infections in immunosuppressed adult mice.

Five strains of adult mice were immunosuppressed with the synthetic glucocorticosteroid dexamethasone (DEX), administered either orally or intraperitoneally. The strains of mice used were C57BL/6N, DBA/2N, CBA, C3H/HeN, and BALB/cAnN. All mice were evaluated for susceptibility to Cryptosporidium parvum after intragastric inoculation with 10(6) oocysts per mouse. The DBA/2N, CBA, C3H/HeN, and BALB/cAnN mice given 0.25 micrograms of DEX per g per day orally (the dose and route previously used to infect rats with C. parvum) failed to develop chronic infections. However, the C57BL/6N mice sustained light infections during the entire 28-day experiment. The five strains of mice were also administered DEX intraperitoneally at concentrations ranging from 62.5 to 500 micrograms/day. Only the C57BL/6N mice given DEX at 125 micrograms/day developed chronic infections which persisted over 10 weeks, suggesting that the genetic background of the mouse plays a role in determining susceptibility to cryptosporidosis following immunosuppression with DEX. We believe that the C57BL/6N mouse model will prove to be superior to other animal models for evaluating potential anticryptosporidial agents, as well as for elucidating the immunological defects that allow C. parvum to establish chronic infections, because of cost effectiveness and ease in maintenance, breeding, and handling. We also evaluated the C3H/HeJ/beige mouse (lacks natural killer cell activity) and the C57BL/6N mouse maintained on a low-protein diet to induce immunosuppression. Neither of these mice exhibited heavy cryptosporidial infections.     

Rapid determination of haemoglobin A1c and glucose in mice: Strain differences, glucose tolerance tests and the neonatal streptozotocin induced diabetic model

Blood glucose and Haemoglobin A_1c (HbA_1c) levels were evaluated from sequestrated blood samples from mice, using a combination of the Antsense II and DCA-2000 analysers, and using only 6μl whole blood. The difference between fed and fasted blood glucose and HbA_1c concentrations among four strains of mice (inbred C57BL/6N, C3H/HeN, hybrid B6C3F1 and outbred CD-1) was examined, and glucose tolerance was further evaluated in each strain by an intraperitoneal glucose tolerance test (IPGTT) using this apparatus. There was considerable variation between fed and fasted glucose and HbA_1c concentrations, with C3H/HeN mice being the most glucose tolerant and CD-1 mice the least glucose tolerant. These findings did not contradict previous observations. A time-course study was also carried out of the levels of blood glucose and HbA_1c of mice with experimentally induced diabetes produced by streptozotocin (STZ). STZ-induced diabetic mice (C57BL/6N, B6C3F1 and CD-1) displayed a transient hyperglycaemia with onset at 2–6 h post-dose, with a return to values in the hypoglcyaemic range 8–12 h later. A further rise in blood glucose was noted at 24 h (C57BL/6N and CD-1 mice), and four days after treatment (B6C3F1 mice). These findings were in agreement with previous observations in rats. HbA_1c levels were significantly elevated at three, five or nine days after treatment in CD-1, C57BL/6N and 1360171, respectively, and parallel the glycaemic changes. In contrast, there were no changes in blood glucose or HbA_1c of C3H/HeN mice. It is considered that the combination of the DCA-2000 and Antsense II analysers give rapidly valid and satisfactory HbA_1c/blood glucose results in mice with only a small amount of blood.     

Dual Role of Interleukin-10 in Murine Lyme Disease: Regulation of Arthritis Severity and Host Defense

In the murine model of Lyme disease, C3H/He mice exhibit severe arthritis while C57BL/6N mice exhibit mild lesions when infected with Borrelia burgdorferi. Joint tissues from these two strains of mice harbor similar concentrations of B. burgdorferi, suggesting that the difference in disease severity reflects differences in the magnitude of the inflammatory response to B. burgdorferi lipoproteins. Stimulation of bone marrow macrophages from C3H/HeN mice with the B. burgdorferi lipoprotein OspA resulted in higher-level production of the inflammatory mediators tumor necrosis factor alpha, nitric oxide, and interleukin-6 (IL-6) than that of macrophages from C57BL/6N mice. In contrast, macrophages from C57BL/6N mice consistently produced larger amounts of the anti-inflammatory cytokine IL-10 than did C3H/HeN macrophages. Addition of recombinant IL-10 suppressed the production of inflammatory mediators by macrophages from both strains. IL-10 was found to modulate B. burgdorferi-induced inflammation in vivo, since C57BL/6J mice deficient in IL-10 (IL-10-/-) developed more severe arthritis than wild-type C57BL/6J mice. The increase in arthritis severity was associated with a 10-fold decrease in the number of B. burgdorferi organisms present in ankle tissues from IL-10-/- mice. These findings suggest that in C57BL/6 mice, IL-10-dependent regulation of arthritis severity occurs at the expense of effective control of bacterial numbers.     

Genetic control of resistance to Mycoplasma pulmonis infection in mice.

The differences in susceptibility of various inbred strains of mice to a highly pathogenic strain of Mycoplasma pulmonis CT (T2) has been known for some time. We assessed the genetic control of resistance to T2 infection. Tracheolung lavage samples and lungs of mice were assessed for T2 organisms after intratracheal injection of T2. We found that H-2b (C57BL/6 (B6) and H-2k B10.BR mice were resistant, whereas H-2b A.By, H-2k C3H/Bi, H-2k C3H/HeJ (C3H), and H-2b BALB.B mice were susceptible. We also typed individual B6C3F2 mice for H-2 and for resistance to T2 and observed that resistance to T2 infections is controlled by a single dominant gene not linked to H-2. Histologic examination revealed severe lung lesions typical of M. pulmonis infections in susceptible C3H mice, in contrast to minimal lung lesions in resistant B6 mice. No significant titers of local or systemic antimycoplasma antibodies were detected in either resistant or susceptible mice at 5 days postinfection. Macrophages taken from uninfected B6 or C3H mice failed to inhibit growth of T2 in vitro. However, macrophages from B6 mice did inhibit growth of T2 much better than C3H macrophages when harvested on day 5 of infection. Thus, there is an association between activation of macrophage bactericidal function and genetic resistance to growth of T2 organisms.     

Reactivation of chlamydial genital tract infection in mice.

A model was developed to study chlamydial quiescence in C3H/HeN (C3H) and C57BL/6N (C57) mice following genital tract infection by Chlamydia trachomatis MoPn. Reactivation of chlamydial shedding following immunosuppression indicated that viable MoPn remained in the genital tract for up to 4 or 5 weeks after the apparent clearance of a primary infection. Either cyclophosphamide or cortisone acetate treatment could cause reactivation, but cyclophosphamide was more effective. However, the frequency of reactivation by either drug diminished with time in both mouse strains. Progesterone treatment prior to infection of C57 mice greatly reduced the frequency of reactivation by cyclophosphamide and also correlated with the development of marked fluid accumulation and distension of the uterine horns in the vast majority of those animals. This pathology was apparent by 5 to 7 weeks postinfection and was consistently seen through 110 days postinfection. Neither of these phenomena was observed in C57 mice that had not been treated with progesterone or in C3H mice under any conditions tested. The infecting dose of MoPn did not clearly influence the frequency of reactivation in either inbred strain as defined by this model.     

Central role of toll-like receptor 4 signaling and host defense in experimental pneumonia caused by Gram-negative bacteria

Toll-like receptor 4 (TLR4) has been identified as a receptor for lipopolysaccharide. However, the precise role of TLR4 in regulating gene expression in response to an infection caused by gram-negative bacteria has not been fully elucidated. The role of TLR4 signaling in coordinating gene expression was assessed by gene expression profiling in lung tissue in a mouse model of experimental pneumonia with a low-dose infection of Klebsiella pneumoniae. We analyzed four mouse strains: C57BL/6 mice, which are resistant to bacterial dissemination; 129/SvJ mice, which are susceptible; C3H/HeJ mice, which are susceptible and have defective TLR4 signaling; and their respective control strain, C3H/HeN (intermediate resistance). At 4 h after infection, C57BL/6 and C3H/HeN mice demonstrated the greatest number of genes, with 67 shared induced genes which were TLR4 dependent and highly associated with the resistance phenotype. These genes included cytokine and chemokine genes required for neutrophil activation or recruitment, growth factor receptors, MyD88 (a critical adaptor protein for TLR signaling), and adhesion molecules. TLR4 signaling accounted for over 74% of the gene expression in the C3H background. These data suggest that early TLR4 signaling controls the vast majority of gene expression in the lung in response to an infection caused by gram-negative bacteria and that this subsequent gene expression determines survival of the host.     

Rapid determination of haemoglobin A1c and glucose in mice: Strain differences, glucose tolerance tests and the neonatal streptozotocin induced diabetic model

Blood glucose and Haemoglobin A_1c (HbA_1c) levels were evaluated from sequestrated blood samples from mice, using a combination of the Antsense II and DCA-2000 analysers, and using only 6μl whole blood. The difference between fed and fasted blood glucose and HbA_1c concentrations among four strains of mice (inbred C57BL/6N, C3H/HeN, hybrid B6C3F1 and outbred CD-1) was examined, and glucose tolerance was further evaluated in each strain by an intraperitoneal glucose tolerance test (IPGTT) using this apparatus. There was considerable variation between fed and fasted glucose and HbA_1c concentrations, with C3H/HeN mice being the most glucose tolerant and CD-1 mice the least glucose tolerant. These findings did not contradict previous observations. A time-course study was also carried out of the levels of blood glucose and HbA_1c of mice with experimentally induced diabetes produced by streptozotocin (STZ). STZ-induced diabetic mice (C57BL/6N, B6C3F1 and CD-1) displayed a transient hyperglycaemia with onset at 2–6 h post-dose, with a return to values in the hypoglcyaemic range 8–12 h later. A further rise in blood glucose was noted at 24 h (C57BL/6N and CD-1 mice), and four days after treatment (B6C3F1 mice). These findings were in agreement with previous observations in rats. HbA_1c levels were significantly elevated at three, five or nine days after treatment in CD-1, C57BL/6N and 1360171, respectively, and parallel the glycaemic changes. In contrast, there were no changes in blood glucose or HbA_1c of C3H/HeN mice. It is considered that the combination of the DCA-2000 and Antsense II analysers give rapidly valid and satisfactory HbA_1c/blood glucose results in mice with only a small amount of blood.     

Effect of the host's body genotype and phenotype on the manifestation of the pathogenic properties of the influenza virus

The sensitivity of mice of CBA (H-2k haplotype), C57BL/6 (H-2b haplotype) strains and their hybrids M1 and F2 to the pathogenic influenza A/PR8/34 (H0N1) and nonpathogenic A/Krasnodar/101/59 (H2N2) virus strains was studied. The lethality, virus replication in the lungs, and the thymic index were determined. An increase in the resistance to the pathogenic influenza virus was found in male C57BL/6 and male F1 (CBA X C57BL/6) hybrids in the summer period as compared with winter. Replication of the pathogenic virus in the lungs of mice, in contrast to the nonpathogenic one, was accompanied by marked atrophy of the thymus. The study suggests the existence of a certain association between the resistance to influenza infection and phenotypic changes in the host connected with the weight of the thymus and the presence of mature T-lymphocytes.     

Lps Genotype in the C57 Black Mouse Blackground and its Influence on the Interleukin-6 Response to E. coli Urinary Tract Infection

The present study examined the influence of the mouse Lps genotype on the interleukin-6 (IL-6) and polymorphonuclear leucocyte (PMN) responses to mucosal Escherichia coli infection. Lipopolysaccharide (LPS) responder C57BL/6J (Lpsn, Lpsn) and LPS non-responder C57BL/10ScCr (Lpsd, Lpsd) mice were inoculated intravesically with Escherichia coli Hu734. The secretion of IL-6, the recruitment of PMNs into urine, and the bacterial clearance from the kidneys and bladders were compared between the two mouse strains at 2, 6 and 24 h after infection. The C57BL/6J mice showed a high PMN response and rapid clearance of bacteria from the kidneys and bladders. In the C57BL/10ScCr mice the PMN response was low and infection remained. This supported a role of the Lps genotype in these events. The IL-6 levels remained low after infection in both LPS responder and non-responder mice, but became elevated in the animals which were accidentally traumatized during infection. The IL-6 response to trauma alone was independent of Lps genotype, but the response to trauma and infection combined differed between the mouse strains. The IL-6 response to trauma and infection was more rapid in the C57BL/6J than in the C57B1/10ScCr mice. The traumatized and infected animals did not clear the infection as efficiently as the non-injured animals in both backgrounds. The difference in PMN recruitment and susceptibility of infection between LPS responder and non-responder mice in the C57 Black background followed the pattern previously seen in the C3H mouse background and suggested that these events were under Lps gene control. An effect of the Lps locus on the IL-6 response could be detected only in traumatized and infected animals.     

Cytokine and chemokine transcription profile during Mycoplasma pulmonis infection in susceptible and resistant strains of mice: macrophage inflammatory protein 1beta (CCL4) and monocyte chemoattractant protein 2 (CCL8) and accumulation of CCR5+ Th cells

The progression of murine mycoplasma pneumonia is dependent on T cells and other immune cells. The role of cytokines in immunity are complex, and identifying the network of cytokines produced after infection of mice is essential in dissecting the key cytokine cascades involved mycoplasma disease pathogenesis. In the present study, mRNA expression of 143 different cytokines, chemokines, or receptors were evaluated in lung tissues from both susceptible (BALB/c and C3H/HeN) and resistant (C57BL/6) mice after Mycoplasma pulmonis infection. To accomplish this, membrane-based cDNA microarrays were used to monitor changes mRNA expression in lungs. There was a clear association with disease susceptibility and development of cytokine mRNA expression. In addition to proinflammatory cytokines, mRNA expression of an anti-inflammatory cytokine, interleukin-10, increased with disease severity, suggesting an attempt to moderate the severity of the inflammatory response. Furthermore, it is clear that an array of chemokines produced in susceptible mice could contribute to the recruitment and maintenance of inflammatory cells at the site of disease. In support of this, there was an increase in macrophage inflammatory protein 1beta (MIP-1beta; CCL4) and monocyte chemoattractant protein 2 (MCP-2; CCL8) mRNA levels from mycoplasma-infected mice and a corresponding accumulation of CD4+ Th cells expressing the MIP-1beta/MCP-2 receptor, CCR5, in the lungs of mice. Furthermore, MIP-1beta- and MCP-2-producing cells and CD4+ T cells were found to be in close association in pulmonary lesions. Thus, there was a significant cytokine response associated with disease pathogenesis, and these studies provide important leads and insights into ongoing cytokine- and chemokine-mediated processes in this persistent inflammatory disease.