Modulation of human T cell cytokines by the Mycobacterium tuberculosis -secreted protein Wag31

Samten, Buka; Fannin, Stewart; Sarva, Krishna; Yi, Na; Madiraju, Murty V. V. S.; Rajagopalan, Malini

doi:10.1016/j.tube.2016.09.017

Cited by 9 publications

(6 citation statements)

References 39 publications

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“…Mycobacterium spp. DivIVA, also known as Wag31, was initially characterized as the highly immunogenic antigen Ag84 in Mycobacterium tuberculosis and Mycobacterium leprae strains (119,120). In Mycobacterium species (which, unlike Firmicutes, undergo apical growth [121]), DivIVA is essential (122)(123)(124) and localizes to the septum, cell poles, and branching sites (124)(125)(126)(127).…”

Section: Multiple Functions Of Diviva In Actinobacteriamentioning

confidence: 99%

¡vIVA la DivIVA!

2019

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Reproduction in the bacterial kingdom predominantly occurs through binary fission—a process in which one parental cell is divided into two similarly sized daughter cells. How cell division, in conjunction with cell elongation and chromosome segregation, is orchestrated by a multitude of proteins has been an active area of research spanning the past few decades. Together, the monumental endeavors of multiple laboratories have identified several cell division and cell shape regulators as well as their underlying regulatory mechanisms in rod-shaped Escherichia coli and Bacillus subtilis, which serve as model organisms for Gram-negative and Gram-positive bacteria, respectively. Yet our understanding of bacterial cell division and morphology regulation is far from complete, especially in noncanonical and non-rod-shaped organisms. In this review, we focus on two proteins that are highly conserved in Gram-positive organisms, DivIVA and its homolog GpsB, and attempt to summarize the recent advances in this area of research and discuss their various roles in cell division, cell growth, and chromosome segregation in addition to their interactome and posttranslational regulation.

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Section: Multiple Functions Of Diviva In Actinobacteriamentioning

confidence: 99%

¡vIVA la DivIVA!

2019

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“…Depletion of FipA and PonA1/PonA2 is known to reduce bacterial replication in macrophages and murine infection models, respectively (38,62,63). The recent finding that a C-terminal fragment of and full-length Wag31 induced production of T cell cytokines such as IL-10 and IL-17 suggests a crucial role of cell division proteins in maintenance of bacillus survival during infection (64). The observed reduction in bacillus growth during macrophage infection with the FtsQ depletion strain indicates that FtsQ plays an important role in maintenance of cell division and hence persistent survival of the pathogen during host infection (Fig.…”

Section: Role Of Ftsq In Cell Divisionmentioning

confidence: 99%

Delineating FtsQ-mediated regulation of cell division in Mycobacterium tuberculosis

Jain

Malakar

Khan

et al. 2018

Journal of Biological Chemistry

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Identifying and characterizing the individual contributors to bacterial cellular elongation and division will improve our understanding of their impact on cell growth and division. Here, we delineated the role of , a terminal gene of the highly conserved division cell wall () operon, in growth, survival, and cell length maintenance in the human pathogen (). We found that FtsQ overexpression significantly increases the cell length and number of multiseptate cells. FtsQ depletion in resulted in cells that were shorter than WT cells during the initial growth stages (4 days after FtsQ depletion) but were longer than WT cells at later stages (10 days after FtsQ depletion) and compromised the survival and in differentiated THP1 macrophages. Overexpression of N- and C-terminal FtsQ regions altered the cell length, and the C-terminal domain alone complemented the FtsQ depletion phenotype. MS analyses suggested robust FtsQ phosphorylation on Thr-24, and although phosphoablative and -mimetic mutants rescued the FtsQ depletion-associated cell viability defects, they failed to complement the cell length defects. MS and coimmunoprecipitation experiments identified 63 FtsQ-interacting partners, and we show that the interaction of FtsQ with the recently identified cell division protein SepIVA is independent of FtsQ phosphorylation and suggests a role of FtsQ in modulating cell division. FtsQ exhibited predominantly septal localization in both the presence and absence of SepIVA. Our results suggest a role for FtsQ in modulating the length, division, and survival of cells both and in the host.

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“…In this study, the N-terminal part of Rv2145c was not involved in Rv2145c-mediated IL-10 production and Mtb growth enhancement. Samten B et al reported that Wag31 and its C-terminal domain inhibit anti-CD3 and anti-CD28 antibody-mediated IL-10 and IL-17 production in human T cells ( 41 ), but this study was performed in purified T cells without antigen-presenting cell involvement.…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, Rv2145c induced macrophage activation with elevated IL-10 production ( Figure 1 ). Rv2145c has relatively conserved sequences in both N-terminal and C-terminal regions among the mycobacteria ( 41 ). In this study, the N-terminal part of Rv2145c was not involved in Rv2145c-mediated IL-10 production and Mtb growth enhancement.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium tuberculosis Rv2145c Promotes Intracellular Survival by STAT3 and IL-10 Receptor Signaling

et al. 2021

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Although Mycobacterium tuberculosis (Mtb) is an intracellular pathogen in phagocytic cells, the factors and mechanisms by which they invade and persist in host cells are still not well understood. Characterization of the bacterial proteins modulating macrophage function is essential for understanding tuberculosis pathogenesis and bacterial virulence. Here we investigated the pathogenic role of the Rv2145c protein in stimulating IL-10 production. We first found that recombinant Rv2145c stimulated bone marrow-derived macrophages (BMDMs) to secrete IL-10, IL-6 and TNF-α but not IL-12p70 and to increase the expression of surface molecules through the MAPK, NF-κB, and TLR4 pathways and enhanced STAT3 activation and the expression of IL-10 receptor in Mtb-infected BMDMs. Rv2145c significantly enhanced intracellular Mtb growth in BMDMs compared with that in untreated cells, which was abrogated by STAT3 inhibition and IL-10 receptor (IL-10R) blockade. Expression of Rv2145c in Mycobacterium smegmatis (M. smegmatis) led to STAT3-dependent IL-10 production and enhancement of intracellular growth in BMDMs. Furthermore, the clearance of Rv2145c-expressing M. smegmatis in the lungs and spleens of mice was delayed, and these effects were abrogated by administration of anti-IL-10R antibodies. Finally, all mice infected with Rv2145c-expressing M. smegmatis died, but those infected with the vector control strain did not. Our data suggest that Rv2145c plays a role in creating a favorable environment for bacterial survival by modulating host signals.

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Modulation of human T cell cytokines by the Mycobacterium tuberculosis -secreted protein Wag31

Cited by 9 publications

References 39 publications

¡vIVA la DivIVA!

¡vIVA la DivIVA!

Delineating FtsQ-mediated regulation of cell division in Mycobacterium tuberculosis

Mycobacterium tuberculosis Rv2145c Promotes Intracellular Survival by STAT3 and IL-10 Receptor Signaling

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