Disseminated Mycobacterium avium complex (MAC) is the most common bacterial infection in patients with the acquired immunodeficiency syndrome (AIDS). Three clinical observations are characteristic of MAC-AIDS infection: 1) The severity of the anemia compared to the anemia seen in AIDS without MAC 2) The short survival of patients with MAC-AIDS associated anemia and 3) The lack of any effective treatment for MAC infection. To understand the mechanism for defective erythropoiesis in AIDS patients infected with MAC we studied the effect of sera from these patients in standard hematopoietic colony formation assay in vitro. Only sera from MAC-AIDS patients but not from AIDS alone were inhibitory to erythroid colonies (BFU-E and CFU-E). To pursue the study at the cellular level, assuming that MAC organisms are primary targets to host macrophages, we used two experimental approaches. In the first we infected human monocytes with M. avium serovar 4 and assayed the supernatants in short term bone marrow (BM) cultures. In the second we made liposomes carrying glycopeptidolipid (GLP) specific for the same epitope and added directly to MB cultures. This GPL defines a particular strain commonly isolated in AIDS patients. In both cases we found a selective inhibition on erythroid colonies but not effect or little effect on myeloid colonies (CFU-GM) with liposomes or the entire bacilli respectively. We propose to continue to analyze the cellular interactions and the factors involved in MAC-AIDS defective erythropoiesis by 1) examining the specificity of different serovars and other cell wall components shared by mycobacteria 2) determining the presence of inhibitory factors in supernatants from cultured monocytes from AIDS and MAC-AIDS patients 3) studying the supernatants of human monocytes co-infected in vitro with HIV-MAC 4) purifying and characterizing the inhibitory factor. Identification of the mechanism responsible for the deficient erythropoiesis in MAC infected AIDS patients may help us to gain new insights into the interactions of mycobacteria with cells of the immune system as well as to help to develop new therapeutic strategies in this fatal disease.
