Relationship between virulence of Mycobacterium avium strains and induction of tumor necrosis factor alpha production in infected mice and in in vitro-cultured mouse macrophages

Abstract

We studied the ability of two Mycobacterium avium strains with different virulences to induce tumor necrosis factor alpha (TNF) synthesis by mouse resident peritoneal macrophages (RPM) in vitro in an experiment to look for a possible correlation between virulence and this TNF-inducing capacity. The low-virulence strain, 1983, induced significantly higher production of TNF by RPM than did the high-virulence strain, ATCC 25291. TNF neutralization during culture of infected RPM resulted in enhancement of growth of strain 1983 and had no effect on growth of strain ATCC 25291; TNF treatment of strain ATCC 25291-infected macrophages had no effect on mycobacterial growth. The extent of M. avium growth and the amount of TNF synthesis were independent of the presence of contaminating T cells or NK cells in the macrophage monolayers. Intraperitoneal administration of anti-TNF monoclonal antibodies to BALB/c mice infected intravenously with M. avium 1983 abrogated the elimination of the bacteria in the liver and caused a slight increase in bacterial growth in the spleen. Neutralization of TNF led to a minor increase in the proliferation of M. avium ATCC 25291 in the liver and spleen of BALB/c mice late in infection. Anti-TNF treatment did not affect the growth of the two M. avium strains in BALB/c.Bcg r (C.D2) mice, suggesting that restriction of M. avium growth in these mycobacterium-resistant mice is TNF independent. In conclusion, the capacity of certain avirulent M. avium strains to induce TNF production by macrophages may limit their ability to proliferate both in vitro and in vivo.

Dynamics of immune effector mechanisms during infection with Mycobacterium avium in C57BL/6 mice

“…It has been reported that less virulent mycobacteria are more sensitive to TNF. 71 We found adequate TNF responses in the liver as well as in isolated human or mouse macrophages (data not shown), so given the high influx of neutrophils and macrophages to the spleen from 1 week post infection we would have expected a higher production of inflammatory cytokines. Concomitant induction of anti-inflammatory IL-10 has previously been found to negatively influence the secretion of TNF and IFN-c in response to mycobacterial infection compared with other Gram-positive or Gram-negative microbes in human peripheral blood monocytes.…”

Mycobacterium avium infection in CD14‐deficient mice fails to substantiate a significant role for CD14 in antimycobacterial protection or granulomatous inflammation

“…In CD14+/+ Mw, the highly virulent strain TMC724 always induced less TNF secretion than SE01, the strain of intermediate virulence, regardless of the dose used for stimulation, a ®nding previously reported for other M. avium isolates differing in virulence. 32 Of note, the dose required to elicit in CD14x/x bone marrow-derived Mw a response equivalent to that in CD14+/+ Mw was at least 10-fold higher for both strains tested 6 hr after infection ( Fig. 1a, 1b).…”

“…It has previously been noted that M. avium strains of differing virulence induce secretion of different amounts of TNF from Mw in vivo. 32 Our data extend these ®ndings and show that strains of both high and intermediate virulence induce TNF in a CD14-dependent manner.…”

The Production of Nitric Oxide and Tumor Necrosis Factor by Murine Macrophages Infected with Mycobacterial Strains Differing by Hemolytic Activity

“…3). On the contrary, Sarmento and Appelberg (47) and Eriks and Emerson (22) found that the low-virulence M. avium strains induced more intensive TNF-a production than the high-virulence M. avium bacilli did. However, they were using resident peritoneal or bone marrow-derived macrophages, respectively.…”

“…The microbicidal activity of macrophages against MTB and other mycobacteria has also been shown to be regulated by the TNF-oc alone or in synergy with other cytokines (5, 6,47). Furthermore, TNF-sa production in vivo may lead to granuloma formation, which limits bacterial dissemination within the host (52).…”