Exposure of human peripheral blood mononuclear cells to total lipids and serovar-specific glycopeptidolipids from Mycobacterium avium serovars 4 and 8 results in inhibition of TH1-type responses

Previous studies have suggested that large quantities of bacterial lipids m ay accumulate and persist within host cells during chronic stages of Mycoba cterium avium infections. This study intended to assess the ability of puri fied M. avium lipids to affect TH-l-type responses in human peripheral bloo d mononuclear cells (PBMC) from healthy donors. PBMC were exposed to total lipids and serovar-specific glycopeptidolipids (GPL) extracted from M. aviu m serovars 4 and 8, which have been reported to predominate as opportunisti c infection among AIDS patients. After 24 h exposure to lipids followed by PHA/PMA treatment, IL-2 and IFN-gamma were assayed in the supernatants. Rev erse transcriptase polymerase chain reaction (RT-PCR) was used for a semiqu antitative estimation of mRNA for IL-2 and IFN-gamma in cell pellets at var ious time points. Exposure of PBMC to M. avium total lipids significantly s uppressed PHA/PMA-induced secretion of IL-2 and IFN-gamma as determined by ELISA. The GPL antigens from serovar 4 were more efficient at inhibiting TH -1 responses than GPL from serovar 8. CD4(+) T-lymphocyte enrichment of PBM C demonstrated that suppression by M. avium lipids was intact without the p resence of other cell populations such as monocytes and B-cells. Preliminar y RT-PCR experiments showed that the secretion of TH-1 cytokines was partia lly affected at the transcriptional level. The results obtained showed that M. avium lipids are indeed able to modify the induction of TH-1-type cytok ines by human PBMC, and suggest that accumulation of M avium lipids in the chronic stages of infection may play an important role in the pathogenesis of HIV infection. (C) 2000 Academic Press.