Brodie S, Sasseville V, Simon M, Sehgal P, Desrosiers R, Ringler D; Symposium on Nonhuman Primate Models for AIDS.
J Med Primatol. 1993 Sep-Oct; 22: abstract no. 44.
Division of Pathology, Harvard Medical School, Southborough, MA.
Because alveolar macrophages (Mphi) play a major role in the host defense against inhaled microorganisms and are susceptible targets of lentivirus infection, we investigated if lentiviral infection of M phi alters microbicidal potential. Alveolar Mphi infected with SIVmac were assessed for their ability to kill encapsulated and acapsular strains of Cryptococcus neoformans. For this purpose, rhesus alveolar M phi were obtained from healthy retrovirus-free donors (n = 6) and from SIV-seropositive individuals (n = 25) in different stages of disease (asymptomatic, n = 14; and AIDS, n = 11). We found that phagocytosis was essential for killing of Cryptococcus organisms, and only acapsular organisms were effectively phagocytosed. Furthermore, infection in vitro with SIVmac239 (molecular clone), SIVmac239/316 (Mphi-competent variant of SIVmac239), or SIVmac251 (wildtype isolate) did not affect Mphi-mediated killing of acapsular yeast up to 16 d postinoculation (p < 0.05). In vivo studies showed that alveolar Mphi from individuals with AIDS killed C. neoformans less efficiently (10.4 +/- 2.78% killing) after 2 h, and when stimulated with phorbol myristate, they produced less superoxide anion (O2-; 0.15 +/- 0.02 O2-/h/mg of Mphi protein) than Mphi from uninfected monkeys (21.8 +/- 1.6% killing and 0.29 +/- 0.02 O2-/h/mg of Mphi protein). Killing and O2- release was accentuated in SIV-infected asymptomatic monkeys (25.8 +/- 2.32% killing and 0.40 +/- 0.04 O2-/h/mg of Mphi protein) (p < 0.05) compared to controls. Killing could be partially restored in macrophages from individuals with AIDS by culturing Mphis for 24 h in supernatants from mitogen-stimulated peripheral blood mononuclear cells (PBMCs), obtained from asymptomatic or uninfected monkeys, but not from individuals with AIDS. Furthermore, supernatants from stimulated PBMCs from animals with AIDS had no effect on Mphis from uninfected or asymptomatic individuals. Collectively, these findings suggest that functional aberrations in alveolar Mphis are not directly secondary to virus infection but likely result from a relative absence of stimulatory events in the pulmonary microenvironment in animals with AIDS.
Publication Types:
Keywords:
- Acquired Immunodeficiency Syndrome
- Animals
- Antigens, Fungal
- Cryptococcosis
- Cryptococcus
- Cryptococcus neoformans
- In Vitro
- Lung
- Macaca mulatta
- Macrophages
- Macrophages, Alveolar
- Phagocytosis
- Simian Acquired Immunodeficiency Syndrome
- Simian immunodeficiency virus
- Superoxides
- immunology
Other ID:
UI: 102207773
From Meeting Abstracts