Mycobacterium xenopi multiplies within human macrophages and enhances HIV replication in vitro.
Mycobacterium xenopi can cause opportunistic infections, particularly in persons infected with human immunodeficiency virus type 1 (HIV-1). The primary focus of this effort was to determine if M. xenopi isolates could survive and grow in human peripheral blood macrophage (MPhi), and if these isolates could promote the replication of HIV-1 in vitro. M. xenopi bacilli survived and replicated 10-fold within 48 h in human MPhi while avirulent Mycobacterium smegmatis, did not grow within the MPhi. M. xenopi bacilli when cultured with peripheral blood mononuclear cells enhanced HIV-1 replication 30- and 50-fold with the macrophage-tropic HIV-1(Ba-L) and 50- and 75-fold with T-cell-tropic strain HIV-1(LAI) by 6 days post-infection when compared to M. smegmatis. The enhanced HIV replication was associated with increased production of TNF-alpha. Partial inhibition of HIV-1 induction was observed using a neutralizing anti-TNF-alpha monoclonal antibody, pentoxifylline, and matrix metalloproteinase (MMP) inhibitor I. Similar mechanisms of pathogenesis among mycobacterial species may help elucidate better treatment approaches in HIV co-infected persons.
Swords
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Tuberculosis/Mycobacteriology Branch, Division of TB Elimination, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Guenthner
P C
PC
Birkness
K A
KA
Lal
R B
RB
Dezzutti
C S
CS
Quinn
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FD
D017088:AIDS-Related Opportunistic Infections / Q000382:microbiology; D000583:Amikacin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015683:Gene Products, gag / Q000032:analysis; D015658:HIV Infections / Q000150:complications*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000382:microbiology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D009165:Mycobacterium Infections, Nontuberculous / Q000097:blood / Q000150:complications* / Q000382:microbiology; D019912:Mycobacterium xenopi / Q000254:growth & development* / Q000472:pathogenicity / Q000502:physiology; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D014775:Virus Activation / Q000502:physiology; D014779:Virus Replication / Q000502:physiology*; D054301:gag Gene Products, Human Immunodeficiency Virus
D000900:Anti-Bacterial Agents; D015683:Gene Products, gag; C059827:HIV gag protein p25; D061965:Matrix Metalloproteinase Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D054301:gag Gene Products, Human Immunodeficiency Virus; D000583:Amikacin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9