A Rho GDP Dissociation Inhibitor Produced by Apoptotic T-Cells Inhibits Growth of
Most people who are infected with Mycobacterium tuberculosis (M. tb) have latent tuberculosis infection (LTBI) with protective immunity. Patients with active tuberculosis have severe disease and ineffective immunity. Understanding how LTBI individuals control infection without developing disease provides important insight into the mechanisms of protective immunity against tuberculosis, and this information is essential for development of an effective vaccine. It is known that a lymphocyte population called T-cells contributes significantly to protective immunity against tuberculosis infection. In the current study, using human and murine models of M. tb infection, we found that a soluble factor, Rho GDP dissociation inhibitor (D4GDI), produced by a subpopulation of T-cells (CD4+CD25+Foxp3+) inhibits M. tb growth. We also found that D4GDI induces M. tb genes that are expressed during the non-replicative state. Our results suggest that D4GDI has a previously undescribed positive effect on immunity by enhancing host antimicrobial activity. These findings also may aid in understanding the factors that induce LTBI. Further, this information will facilitate development of improved vaccines and immunotherapeutic strategies to prevent and treat tuberculosis, respectively.
Vyšlo v časopise:
A Rho GDP Dissociation Inhibitor Produced by Apoptotic T-Cells Inhibits Growth of. PLoS Pathog 11(2): e32767. doi:10.1371/journal.ppat.1004617
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004617
Souhrn
Most people who are infected with Mycobacterium tuberculosis (M. tb) have latent tuberculosis infection (LTBI) with protective immunity. Patients with active tuberculosis have severe disease and ineffective immunity. Understanding how LTBI individuals control infection without developing disease provides important insight into the mechanisms of protective immunity against tuberculosis, and this information is essential for development of an effective vaccine. It is known that a lymphocyte population called T-cells contributes significantly to protective immunity against tuberculosis infection. In the current study, using human and murine models of M. tb infection, we found that a soluble factor, Rho GDP dissociation inhibitor (D4GDI), produced by a subpopulation of T-cells (CD4+CD25+Foxp3+) inhibits M. tb growth. We also found that D4GDI induces M. tb genes that are expressed during the non-replicative state. Our results suggest that D4GDI has a previously undescribed positive effect on immunity by enhancing host antimicrobial activity. These findings also may aid in understanding the factors that induce LTBI. Further, this information will facilitate development of improved vaccines and immunotherapeutic strategies to prevent and treat tuberculosis, respectively.
Zdroje
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