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Differential tumor necrosis factor alpha production in simian immunodeficiency virus-infected rhesus macaques
G W Newman1, D L Adams, J N Maslow
1Department of Microbiology and Immunology, Morehouse School of Medicine, Atlanta, Georgia 30310, USA. newmang@msm.edu
Abstract:
Mycobacterium avium infections are the third most common opportunistic infection in patients with AIDS. Simian immunodeficiency virus (SIV)-infected rhesus macaques naturally acquire M. avium infections from the environment, and their clinical symptoms are similar to those observed in AIDS patients. We characterized concurrent infection with SIV and M. avium in monkeys on the basis of the growth of the bacteria in macrophages (Mphis) from rhesus macaques and the ability of M. avium to induce SIV replication and tumor necrosis factor alpha (TNF-alpha) production. The simian M. avium isolate grew significantly better than did an isolate from an AIDS patient or a chicken isolate (P = .001); it induced significantly more TNF-alpha production in Mphis from SIV-positive and SIV-negative monkeys than did the isolate from an AIDS patient (P = .013). No significant increase in SIV replication was seen in the M. avium isolates, and no correlation was found between increased SIV replication and increased TNF-alpha production. In addition, Mphis from monkeys infected with M. avium during late-stage SIV disease produced less TNF-alpha when stimulated with virulent M. avium.
Insights
Simian immunodeficiency virus (SIV) and Mycobacterium avium coinfection in macaques mimics human AIDS opportunistic infections. The simian M. avium strain grows better in macrophages and induces more TNF-alpha than human strains.
Area of Science:
- Immunology
- Virology
- Microbiology
Background:
- Mycobacterium avium is a common opportunistic infection in AIDS patients.
- Simian immunodeficiency virus (SIV)-infected macaques serve as a model for AIDS, naturally acquiring M. avium infections.
- Clinical manifestations in these macaques resemble those in human AIDS patients.
Purpose of the Study:
- To characterize concurrent SIV and M. avium infection in rhesus macaques.
- To assess M. avium's growth in macrophages and its effect on SIV replication and TNF-alpha production.
Main Methods:
- Culturing M. avium isolates (simian, AIDS patient, chicken) in rhesus macaque macrophages.
- Measuring bacterial growth, SIV replication, and TNF-alpha production.
- Comparing responses between SIV-positive and SIV-negative monkeys.
Main Results:
- The simian M. avium isolate exhibited significantly greater growth in macrophages compared to isolates from an AIDS patient or chicken (P = .001).
- The simian isolate induced significantly higher TNF-alpha production in macrophages from both SIV-positive and SIV-negative monkeys than the AIDS patient isolate (P = .013).
- No significant increase in SIV replication was observed, and no correlation was found between SIV replication and TNF-alpha production. Macrophages from late-stage SIV-infected monkeys produced less TNF-alpha when stimulated with virulent M. avium.
Conclusions:
- Simian M. avium strains possess distinct growth and inflammatory properties compared to human or avian strains.
- M. avium infection does not appear to directly enhance SIV replication in this model.
- Late-stage SIV infection may impair the host's inflammatory response to M. avium.
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