Immune responsiveness in Mycobacterium avium-infected mice: changes in the proportion of T cell subsets and antibody production during the course of infection (original) (raw)
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Infection and Immunity, 2000
After infection with a low-virulence strain of Mycobacterium avium, C57BL/6 and C57BL/10 mice had clear differences in the control of the infection in their livers and spleens. This difference in susceptibility was not associated with differences in the H-2 complex. It was dependent on the activity of CD4 ؉ T cells but unrelated to the ability of these cells to secrete gamma interferon or to the development of delayed-type hypersensitivity responses at 3 weeks of infection. It was associated with lower total numbers of CD4 ؉ cells present in infected spleens and was related to an earlier induction of protective T cells, as measured by adoptive-transfer assays. These data further strengthen the notion of gamma-interferon-independent mechanisms of protection against mycobacteria.
Microbiology (Reading, England), 2002
BALB/c mice exposed intranasally (i.n.), intradermally (i.d.) or intraperitoneally (i.p.) to low doses of Mycobacterium avium (20 c.f.u. at three different times two weeks apart) showed an increased resistance to a subsequent high-dose (10(5) c.f.u.) infection. I.n.-exposed mice had few mycobacteria in the tissues (>100 c.f.u.) and showed an expansion of CD4(+) T cells associated with overproduction of IL-12 and IFN-gamma, but not IL-4 and IgG antibodies. Parenterally (i.p. and i.d.) exposed animals showed c.f.u. numbers higher than i.n.-exposed mice, together with overproduction of IL-12, IFN-gamma and IL-4 in the case of i.p.-exposed mice, and of IL-12, IFN-gamma and IgG2a and IgG1 antibodies in the case of i.d.-exposed mice. Low-dose exposures were not contained by athymic BALB/c nude mice; however, naive nude mice reconstituted with i.n.-primed CD4(+) T cells of BALB/c mice were protected against high-dose infection, indicating that CD4(+) T cells are essential to control eve...
Mycobacterium avium infection in BALB/c and SCID mice
Journal of Medical Microbiology, 1999
BALB/c and severe combined immunodeficient (SCID) mice were inoculated intraperitoneally with Mycobacterium avium and the numbers of cfu were monitored for 70 days in spleen, liver, lung, kidney, brain and peritoneum. While BALB/c mice formed typical granulomas and controlled bacterial growth in organs, a delay in development of lesions and a modest containment of infection were observed in SCID mice. In the spleen of BALB/c mice, in which bacterial growth was contained, macrophages (Me) and natural killer (NK) cell numbers increased 24.2 times and T-and B-cell numbers increased 31.8 times after 42 days of infection; conversely, a low recruitment of mononuclear cells was observed in the spleen of SCID mice, where M. avium proliferated efficiently. Unlike visceral organs, a pronounced decrease in the number of cfu was observed in the peritoneum of BALB/c mice, concomitantly with a 331.7-fold increase in Me and NK cells and a 39.1-fold increase in T and B cells. In the peritoneum of SCID mice only a bacteriostatic effect was observed despite a 356.7-fold increase in Me and NK cells and a 222.3-fold increase in T and B cells. These results suggest that while an intact immune response can efficiently control M. avium infection in the spleen and peritoneum of BALB/c mice, cells of the innate immune system such as Me and NK cells play a role in the containment of bacterial growth in the peritoneum, but not spleen, of SCID mice.
Infection and immunity, 1999
The role of CD8(+) T cells was evaluated in a mouse model of disseminated Mycobacterium avium infection. C57BL/6J and C57BL/6Jbeta2-/- (beta2-/-) mice were infected intravenously, and the number of viable bacteria in each liver and spleen was determined. No significant difference between the number of bacteria in the two strains of mice was observed at 2, 4, 6, and 8 weeks after infection. Histopathological examination of granulomas from C57BL/6J and beta2-/- mice did not show any difference either in the number of organisms per granuloma or in the size of the granulomas. Investigation of the cytokine profile in the spleen demonstrated that the beta2-/- strain of mice produced a significantly lower amount of gamma interferon at 8 weeks after infection and significantly increased concentrations of tumor necrosis factor alpha compared with that from the wild-type mouse. Interleukin-12 and transforming growth factor beta1 levels did not differ between the two strains of mice at 2, 4, 6...
Infection and Immunity, 1979
Resistance and susceptibility to mycobacterial infection in the Biozzi high and low lines of mice which were genetically selected for their responses to heterologous erythrocytes have been found to be related to the innate ability of nonimmune macrophages to kill or inhibit the growth of the organisms during the first two weeks after infection and to their ability to mount specific and nonspecific immune responses. High antibody-producer mice were more capable of expressing cell-mediated immune parameters than low antibody-producer mice. A direct relationship was observed between the ability of bacteria (BCG vaccine) to multiply inside the reticuloendothelial system and the development of cell-mediated immunity, as measured by the delayed local reaction at the injection site, the lymphoproliferative response in the draining nodes, the tuberculin delayed-type hypersensitivity, the acquired resistance, and the adjuvant effect after BCG inoculation. In high line mice, apart from the in...
Induction and expression of protective T cells during Mycobacterium avium infections in mice
Clinical & Experimental Immunology, 2008
M'cobacterium atium is an opportunistic pathogen that infects individuals suffering from chronic lung disease or immunocompromised patients such as AIDS patients. Here we show that a highly virulent isolate of M. avium proliferated as extensively in T cell deficient as in immunocompetent mice. T cell deficient mice allowed a progressive growth of a less virulent AIDS-derived isolate of M. arium while immunocompetent mice arrested the growth of this isolate. Adoptive transfer of T cell enriched spleen cells between congenic strains of mice differing at the Bcg/Ity/Lsh locus showed that only naturally resistant BALB/c.BCgr (C.D2) mice infected with the highly virulent strain of M. arium or the naturally susceptible BALB/c mice infected with the lower virulence isolate developed protective T cells and that these cells only mediated protection when transferred to naturally susceptible, but not to naturally resistant, mice. Both strains of M. avium proliferated in bone marrow-derived macrophages cultured in titro and they were both susceptible to the bacteriostatic effects induced in the macrophages by crude lymphokines produced by concanavalin A-stimulated spleen cells.
Immunology, 1997
Disseminated infection caused by organisms of Mycobacterium avium complex is common in acquired immune deficiency syndrome (AIDS) patients. M. avium is an intracellular bacterium that multiplies within macrophages. We examined the effect of M. avium infection on the T‐helper cell response in C57/BL/6 black mice. At weekly intervals, CD4+ T‐cells were isolated from spleens and lines were created. T‐cell lines were exposed to sonicated M. avium in the presence of feeder cells and macrophages and the supernatant were collected to measure the concentrations of interferon‐γ (IFN‐γ and interleukin‐10 (IL‐10). Production of IFN‐γ in CD4+ T‐cells obtained from uninfected mice did not vary significantly during the 5 weeks. Levels of IFN‐γ produced by T‐cell lines of infected mice were similar to the control mice during the first 2 weeks but significantly reduced (approximately 30 ng/ml) thereafter. In contrast, production of IL‐10 by T‐cell lines of infected mice was in a range of 190 to 342...
Immunology and Cell Biology, 2002
Mycobacterium avium strain 104 was chosen as the M. avium isolate to sequence, as it is virulent to humans, stable and readily transfectable. As this strain has not been widely studied we sought to investigate the pattern of 104 infection in mice. Bacterial growth and the immune response generated were compared with infection with the low virulence M. avium strain 100, and the high virulence common laboratory strain, 101. Mycobacterium avium strains 104 and 101 grew progressively within mice, while strain 100 was gradually cleared. Strains 104 and 101 induced strong T cell activation and spleen cell cultures produced similar levels of IFN-γ. In mice infected with strain 100 no significant T cell activation or IFN-γ production was measured. Further, mice infected with strain 104 or 101 also displayed comparable inflammatory responses and similar granuloma formation, while only minimal inflammation was seen in mice infected with strain 100. Strains 101 and 104 also grew in a similar fashion in bonemarrow-derived macrophages and induced significant levels of TNF and nitric oxide. Thus infection with M. avium strain 104 induced an immunological response comparable to M. avium strain 101 and, with the availability of its sequence, should be a useful tool for designing new vaccines or drugs therapies to treat the increasing incidence of M. avium infection in humans.
Clinical & Experimental Immunology, 2008
We have investigated the effect of inflammation on host resistance against infection by Mycobacterium avium, an atypical mycobacteria species that is responsible for life-threatening opportunistic infections in AIDS patients. Inflammation was induced in BALB/c mice by two intraperitoneal injections of mineral oil (Freund's incomplete adjuvant, FIA). The BALB/c strain was chosen because it is naturally susceptible to Myco. avium infection. One week after the second FIA injection, the BALB/c mice were infected intravenously with 2-6 x 106 Myco. avium bacilli; at this time, the mice showed systemic granulocytosis because of the FIA injections. The kinetics of the murine infection was determined during 3 months by quantification of Myco. avium loads in the major target organs (liver and spleen) of the mycobacteria. The FIA treatment resulted in a significant decrease in the growth of Myco. avium in the infected BALB/c mice. This enhancement in host resistance to Myco. avium infection lasted for 2-3 months. In contrast with BALB/c animals, C3H mice (naturally resistant to Myco. avium infection) did not show an increased anti-Myco. avium action in association with the FIA treatment. The antimycobacterial effect of the FIA injections in BALB/c mice was compared with that produced by the injection of mycobacterial antigens (heat-killed Myco. tuberculosis) added to the mineral oil (i.e. Freund's complete adjuvant, FCA). The FCA treatment resulted in strong and sustained enhancements in the microbicidal capacities of BALB/c, and also of C3H mice. Data obtained with mutant athymic BALB/c mice revealed that the anti-Myco. avium effect of the FCA treatment was T cell-dependent. Our results indicate that: (i) non-immune inflammatory stimulation (FIA) of Myco. avium-susceptible hosts is able to cause a significant, albeit transient, increase in the resistance to Myco. avium infection; (ii) this protective effect is enhanced if heat-killed mycobacteria are added to the phlogistic agent (FCA), i.e. if a T cell-dependent response is induced; and (iii) systemic increase in the number of circulating granulocytes may help host defence against Myco. avium infection.