The state of maturation of monocytes into macrophages determines the effects of IL-4 and IL-13 on HIV replication.

Naif, Hassan M.; Li, S; Ho-Shon, Michael; Mathijs, Jean Marie; Williamson, Peter; Cunningham, Anthony L.

doi:10.4049/jimmunol.158.1.501

Cited by 55 publications

(1 citation statement)

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“…Another study showed that IL-4 stimulation enhanced transcription that is mediated by IL-4 stimulated NF-κB nuclear translocation. Further, they also state that IL-4 and IL-13 inhibited HIV replication at the transcriptional level in monocyte-derived macrophages after 3 to 5 days of adherence to the surface of plastic culture plates ( 49 ). Interestingly, it has been observed that IL-4 favored the replication of T-tropic (X4) virus as compared to M-tropic (R5) replication ( 50 ), favoring X4 virus generation.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium tuberculosis EspR modulates Th1-Th2 shift by transcriptionally regulating IL-4, steering increased mycobacterial persistence and HIV propagation during co-infection

Yandrapally,

Agarwal,

Chatterjee

et al. 2023

Front. Immunol.

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Mycobacterium tuberculosis (Mtb) and HIV are known to mutually support each other during co-infection by multiple mechanisms. This synergistic influence could be either by direct interactions or indirectly through secreted host or pathogen factors that work in trans. Mtb secretes several virulence factors to modulate the host cellular environment for its persistence and escaping cell-intrinsic immune responses. We hypothesized that secreted Mtb transcription factors that target the host nucleus can directly interact with host DNA element(s) or HIV LTR during co-infection, thereby modulating immune gene expression, or driving HIV transcription, helping the synergistic existence of Mtb and HIV. Here, we show that the Mtb-secreted protein, EspR, a transcription regulator, increased mycobacterial persistence and HIV propagation during co-infection. Mechanistically, EspR localizes to the nucleus of the host cells during infection, binds to its putative cognate motif on the promoter region of the host IL-4 gene, activating IL-4 gene expression, causing high IL-4 titers that induce a Th2-type microenvironment, shifting the macrophage polarization to an M2 state as evident from CD206 dominant population over CD64. This compromised the clearance of the intracellular mycobacteria and enhanced HIV propagation. It was interesting to note that EspR did not bind to HIV LTR, although its transient expression increased viral propagation. This is the first report of an Mtb transcription factor directly regulating a host cytokine gene. This augments our understanding of the evolution of Mtb immune evasion strategies and unveils how Mtb aggravates comorbidities, such as HIV co-infection, by modulating the immune microenvironment.

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Section: Discussionmentioning

confidence: 99%

Mycobacterium tuberculosis EspR modulates Th1-Th2 shift by transcriptionally regulating IL-4, steering increased mycobacterial persistence and HIV propagation during co-infection

Yandrapally,

Agarwal,

Chatterjee

et al. 2023

Front. Immunol.

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Human monocyte/macrophage adhesion, macrophage motility, and IL-4-induced foreign body giant cell formation on silane-modified surfacesin vitro

Jenney

DeFife

Colton

et al. 1998

J. Biomed. Mater. Res.

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A cytokine-based, in vitro model of foreign body giant cell (FBGC) formation was utilized to examine the effect of biomaterial surface chemistry on the adhesion, motility, and fusion of monocytes and macrophages. Human monocytes were cultured for 10 days on 14 different silane-modified glass surfaces, during which time the cells assumed the macrophage phenotype. The adhesion of monocytes and macrophages during the culture period decreased by an average of approximately 50%, with the majority of cell loss observed during days 1-3. Most important, the adhesion of monocytes and macrophages was surface independent except for two surfaces containing terminal methyl groups, which decreased adhesion levels. Interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were added to the medium to induce FBGC formation and enhance macrophage adhesion, respectively. Surprisingly, GM-CSF decreased long-term monocyte/macrophage adhesion. IL-4-induced FBGC density was strongly influenced by the surface carbon content, as determined by X-ray photoelectron spectroscopy (XPS). In contrast, contact angle and surface energy displayed no correlation with FBGC formation. The motility of adherent macrophages, as measured by time-lapse confocal microscopy, was not affected significantly by differences in surface chemistry or the addition of cytokines. The surface dependence of FBGC formation is hypothesized to be the result of varying levels of silane-derived surface carbon.

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IL-13 acts on macrophages to block the completion of reverse transcription, inhibit virus production, and reduce virus infectivity

Montaner

Bailer

Gordon³

1997

Journal of Leukocyte Biology

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The state of maturation of monocytes into macrophages determines the effects of IL-4 and IL-13 on HIV replication.

Cited by 55 publications

References 0 publications

Mycobacterium tuberculosis EspR modulates Th1-Th2 shift by transcriptionally regulating IL-4, steering increased mycobacterial persistence and HIV propagation during co-infection

Mycobacterium tuberculosis EspR modulates Th1-Th2 shift by transcriptionally regulating IL-4, steering increased mycobacterial persistence and HIV propagation during co-infection

Human monocyte/macrophage adhesion, macrophage motility, and IL-4-induced foreign body giant cell formation on silane-modified surfacesin vitro

IL-13 acts on macrophages to block the completion of reverse transcription, inhibit virus production, and reduce virus infectivity

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