Mycobacterium avium complex promotes recruitment of monocyte hosts for HIV-1 and bacteria.
In lymphoid tissues coinfected with Mycobacterium avium complex (MAC) and HIV-1, increased viral replication has been observed. This study investigates the role of MAC in perpetuating both infections through the recruitment of monocytes as potential new hosts for bacteria and HIV-1. Increased numbers of macrophages were present in the lymph nodes of patients with dual infection as compared with lymph nodes from HIV(+) patients with no known opportunistic pathogens. In a coculture system, monocyte-derived macrophages were treated with HIV-1 or M. avium and its constituents to further define the mechanism whereby MAC infection of macrophages initiates monocyte migration. Monocyte-derived macrophages treated with bacteria or bacterial products, but not HIV-1, induced a rapid 2- to 3-fold increase in recruitment of monocytes. Pretreatment of the monocytes with pertussis toxin inhibited the migration of these cells, indicating a G protein-linked pathway is necessary for induction of chemotaxis and thus suggesting the involvement of chemokines. Analysis of chemokine mRNA and protein levels from M. avium-treated cultures revealed MAC-induced increases in the expression of IL-8, macrophage-inflammatory protein (MIP)-1alpha, and MIP-1beta with donor-dependent changes in monocyte chemotactic protein-1. Pyrrolidine dithiocarbamate, an antioxidant, inhibited the activation of NF-kappaB and significantly diminished the MAC-induced chemotaxis, concurrently lowering the levels of monocyte chemotactic protein-1 and MIP-1beta. These data demonstrate that MAC induces macrophage production of multiple chemotactic factors via NF-kappaB to promote monocyte migration to sites of MAC infection. In vivo, opportunistic infection may act as a recruitment mechanism in which newly arrived monocytes serve as naive hosts for both MAC and HIV-1, thus perpetuating both infections.
Hale-Donze
Hollie
H
Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, and Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Greenwell-Wild
Teresa
T
Mizel
Diane
D
Doherty
T Mark
TM
Chatterjee
Delphi
D
Orenstein
Jan M
JM
Wahl
Sharon M
SM
D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D002630:Chemotactic Factors / Q000032:analysis / Q000096:biosynthesis; D015658:HIV Infections / Q000276:immunology / Q000382:microbiology / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000821:virology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000382:microbiology / Q000821:virology; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000382:microbiology* / Q000821:virology*; D015269:Mycobacterium avium Complex / Q000276:immunology* / Q000472:pathogenicity; D016328:NF-kappa B / Q000502:physiology; D009894:Opportunistic Infections / Q000276:immunology / Q000382:microbiology / Q000821:virology
D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D002630:Chemotactic Factors; D019402:Macrophage Inflammatory Proteins; D016328:NF-kappa B