Induction of Tumor Necrosis Factor Alpha (TNFα) and Enhancement of HIV‐1 Replication in the J22HL60 Cell Line by Mycoplasma penetrans

Abstract

Mycoplasma penetrans isolated from clinical specimens of AIDS patients showed potent activity in tumor necrosis factor alpha (TNFα) production in THP‐1, U937 and J22HL60 cell lines, and in the enhancement of HIV‐1 replication in a dormantly‐infected J22HL60 cell line as compared with the activities of other mycoplasmas. Both activities were found in the methanol layer but not in the chloroform layer of the membrane extracted by the Bligh‐Dyer method. TNFα production was observed in the peritoneal macrophages from both lipopolysaccharide‐responsive and ‐unresponsive mouse strains, and was not inhibited by polymyxin B. The induction of TNFα production and enhancement of HIV‐1 replication were strongly inhibited by Concanavalin A‐Sepharose. The inhibitory effect of Concanavalin A‐Sepharose was partially prevented by sugars in the order methyl‐α‐D‐mannopyranoside and methyl‐α‐D‐glucopyranoside but not methyl‐α‐D‐galactopyranoside. Anti‐human TNFα antibody, however, did not reduce the activity of the methanol layer to enhance HIV‐1 replication, suggesting that the methanol layer could enhance HIV‐1 replication directly. These results suggest that the carbohydrate derived from M. penetrans might be responsible for the progression of HIV‐1 infection.

Complexity of the Mycoplasma fermentans M64 Genome and Metabolic Essentiality and Diversity among Mycoplasmas

“…The detection of this species in the peripheral blood lymphocytes and urine of AIDS patients in a previous study suggested that it might have the ability to act as polyclonal activators of both T and B lymphocytes to stimulate the replication of HIV. It is thought to behave as a cofactor or immunomodulator in HIV-related diseases [39]. M. fermentans might be a systemic pathogen, causing fatal disease owing to the infection of the bone marrow in non-HIV-infected patients [40].…”

Lipid‐associated membrane proteins of Mycoplasma fermentans and M. penetrans activate human immunodeficiency virus long‐terminal repeats through Toll‐like receptors

“…These findings indicate increased rates of HIV replication, probably through NF‐κB‐mediated regulation of the HIV LTR. TNF‐α induced by mycoplasma had been thought to induce NF‐κB and HIV replication; however, anti‐TNF‐α immunoglobulin failed to inhibit the enhancement of HIV replication by mycoplasma 18 . Although activation of NF‐κB has been implicated in the mycoplasma‐induced enhancement of HIV replication, the receptor(s) and the pathways of signal transduction via NF‐κB have not been clearly defined.…”

Molecular Biology and Pathogenicity of Mycoplasmas

“…Mycoplasmal products induce cytokines in cells from C3H/HeJ mice that respond poorly to LPS. Furthermore, cytokine induction is not inhibited by the LPS inhibitor polymyxin B (178,201,352,353). The results also show that the same Mycoplasma species may carry several cytokine-inducing molecules that are not necessarily identical to the mycoplasmal mitogenic elements.…”

“…In addition, extraction of M. penetrans membranes with chloroform-methanol yielded, in the methanol layer, a carbohydrate-containing molecule capable of triggering TNF-␣ in murine cell lines (201). The activity of this molecule was inhibited by ConAsepharose but not by the LPS inhibitor polymyxin B. Appar-ently, M. penetrans lipoproteins (352) and the carbohydratecontaining factor (201) that induced cytokine differ from the mitogenic capsular glycolipid of M. penetrans (48), which was unable to elicit IL-1␤ or TNF-␣ in murine splenocytes and was inhibited by polymyxin B.…”