Low expression of antigen-presenting and costimulatory molecules by lung cells from tuberculosis patients

Flores-Batista, V.C.S.; Boéchat, Neio; Lago, Patrícia M.; Lazzarini, Luiz Claudio Oliveira; Pessanha, L.R.; Almeida, Alexandre S. de; Mafort, Thiago Thomáz; Kritski, Afrânio Lineu; Ho, John L.; Silva, José Roberto Lapa e

doi:10.1590/s0100-879x2006005000141

Cited by 9 publications

(4 citation statements)

References 36 publications

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“…Moreover, there have been only a few conflicting reports on group I CD1 expression on APC in lungs and/or lymph nodes from patients affected by TB (4,8,23). Thus, if group I CD1-restricted T lymphocytes contribute to the effective defense against M. tuberculosis (12), the inhibition of CD1 expression might allow M. tuberculosis to effectively evade T-cell surveillance during infection in vivo.…”

Section: Discussionmentioning

confidence: 99%

Mycobacteria Exploit p38 Signaling To Affect CD1 Expression and Lipid Antigen Presentation by Human Dendritic Cells

et al. 2009

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Group I CD1 proteins are specialized antigen-presenting molecules that present both microbial and self lipid antigens to CD1-restricted ␣/␤ T lymphocytes. The production of high levels of gamma interferon and lysis of infected macrophages by lipid-specific T lymphocytes are believed to play pivotal roles mainly in the defense against mycobacterial infections. We previously demonstrated that Mycobacterium tuberculosis and bacillus Calmette-Guérin (Mycobacterium bovis BCG) induce human monocytes to differentiate into CD1 ؊ dendritic cells (DC), which cannot present lipid antigens to specific T cells. Here, we show that in human monocytes mycobacteria trigger phosphorylation of p38 mitogen-activated protein kinase to inhibit CD1 expression in DC derived from infected monocytes. Pretreatment with a specific p38 inhibitor renders monocytes insensitive to mycobacterial subversion and allows them to differentiate into CD1 ؉ DC, which are fully capable of presenting lipid antigens to specific T cells. We also report that one of the pathogen recognition receptors triggered by BCG to activate p38 is complement receptor 3 (CR3), as shown by reduced p38 phosphorylation and partial reestablishment of CD1 membrane expression obtained by CR3 blockade before infection. In conclusion, we propose that p38 signaling is a novel pathway exploited by mycobacteria to affect the expression of CD1 antigen-presenting cells and avoid immune recognition.

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Section: Discussionmentioning

confidence: 99%

Mycobacteria Exploit p38 Signaling To Affect CD1 Expression and Lipid Antigen Presentation by Human Dendritic Cells

et al. 2009

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“…It has been shown that TB patients have significantly lower HLA-DR expressing cells, which may negatively affect T-cell immune responses and thus facilitate the disease progression [21]. For this reason Dzherelo appears to have a positive effect on a subset of activated T lymphocytes which may favorably influence the treatment outcome.…”

Section: Discussionmentioning

confidence: 99%

Effect of oral immunomodulator Dzherelo in TB/HIV co-infected patients receiving anti-tuberculosis therapy under DOTS

Nikolaeva

Maystat

Pylypchuk³

et al. 2008

International Immunopharmacology

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“…Consistently, Bhatt et al reported that B7.1 and B7.2 (the murine homologs of CD80 and CD86) knockout mice are more susceptible to M. tuberculosis infection and that the B7 receptor signaling pathway is critical for long-term containment of infection within lung granulomas (Bhatt et al, 2009). In another study, cells recovered from induced sputum from patients with tuberculosis and controls were analyzed, and it was observed that cells from the infected patients had lower expression levels of co-stimulatory molecules (CD80 and CD86) (Flores-Batista et al, 2007). Decreased expression of these molecules, which are involved in antigen presentation and T-cell activation, in patients could lead to decreased T-cell recognition during M. tuberculosis infection.…”

Section: Discussionmentioning

confidence: 99%

Simvastatin Enhances the Immune Response Against Mycobacterium tuberculosis

et al. 2019

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Tuberculosis remains a serious threat worldwide. For this reason, it is necessary to identify agents that shorten the duration of treatment, strengthen the host immune system, and/or decrease the damage caused by the infection. Statins are drugs that reduce plasma cholesterol levels and have immunomodulatory, anti-inflammatory and antimicrobial effects. Although there is evidence that statins may contribute to the containment of Mycobacterium tuberculosis infection, their effects on peripheral blood mononuclear cells (PBMCs) involved in the immune response have not been previously described. Using PBMCs from 10 healthy subjects infected with M. tuberculosis H37Rv, we analyzed the effects of simvastatin on the treatment of the infections in an in vitro experimental model. Direct quantification of M. tuberculosis growth (in CFU/mL) was performed. Phenotypes and cell activation were assessed via multi-color flow cytometry. Culture supernatant cytokine levels were determined via cytokine bead arrays. The induction of apoptosis and autophagy was evaluated via flow cytometry and confocal microscopy. Simvastatin decreased the growth of M. tuberculosis in PBMCs, increased the proportion of NKT cells in culture, increased the expression of co-stimulatory molecules in monocytes, promoted the secretion of the cytokines IL-1β and IL-12p70, and activated apoptosis and autophagy in monocytes, resulting in a significant reduction in bacterial load. We also observed an increase in IL-10 production. We did not observe any direct antimycobacterial activity. This study provides new insight into the mechanism through which simvastatin reduces the mycobacterial load in infected PBMCs. These results demonstrate that simvastatin activates several immune mechanisms that favor the containment of M. tuberculosis infection, providing relevant evidence to consider statins as candidates for host-directed therapy. They also suggest that future studies are needed to define the roles of statin-induced anti-inflammatory mechanisms in tuberculosis treatment.

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Low expression of antigen-presenting and costimulatory molecules by lung cells from tuberculosis patients

Cited by 9 publications

References 36 publications

Mycobacteria Exploit p38 Signaling To Affect CD1 Expression and Lipid Antigen Presentation by Human Dendritic Cells

Mycobacteria Exploit p38 Signaling To Affect CD1 Expression and Lipid Antigen Presentation by Human Dendritic Cells

Effect of oral immunomodulator Dzherelo in TB/HIV co-infected patients receiving anti-tuberculosis therapy under DOTS

Simvastatin Enhances the Immune Response Against Mycobacterium tuberculosis

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