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Unexpected Role for IL-17 in Protective Immunity against Hypervirulent HN878 Infection


Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), infects one third of the world's population. Among these infections, clinical isolates belonging to the W-Beijing are emerging, representing about 50% of Mtb isolates in East Asia, and about 13% of all Mtb isolates worldwide. In animal models, infection with W-Beijing strain, Mtb HN878, is considered “hypervirulent” resulting in increased mortality. The proinflammatory cytokine Interleukin (IL)-17 is thought to be dispensable for primary immunity against Mtb infection. We report here that while IL-17 is dispensable for protection against infection with lab adapted Mtb strains such as H37Rv, or less virulent Mtb clinical isolates such as Mtb CDC1551, IL-17 is required for early protective immunity against Mtb HN878 infection. The dependence on IL-17 to drive protective immunity against Mtb HN878 is due to the differential ability to induce high levels of IL-1β through a TLR-2-dependent mechanism, driving potent IL-17 responses, induction of the chemokine CXCL-13 and localization of T cells within lung lymphoid follicles for maximal macrophage activation and Mtb control. Together, our data change the existing paradigm that IL-17 is dispensable for primary immunity against Mtb infection, and suggests a differential requirement for IL-17 in protective immunity against some emerging Mtb strains.


Vyšlo v časopise: Unexpected Role for IL-17 in Protective Immunity against Hypervirulent HN878 Infection. PLoS Pathog 10(5): e32767. doi:10.1371/journal.ppat.1004099
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004099

Souhrn

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), infects one third of the world's population. Among these infections, clinical isolates belonging to the W-Beijing are emerging, representing about 50% of Mtb isolates in East Asia, and about 13% of all Mtb isolates worldwide. In animal models, infection with W-Beijing strain, Mtb HN878, is considered “hypervirulent” resulting in increased mortality. The proinflammatory cytokine Interleukin (IL)-17 is thought to be dispensable for primary immunity against Mtb infection. We report here that while IL-17 is dispensable for protection against infection with lab adapted Mtb strains such as H37Rv, or less virulent Mtb clinical isolates such as Mtb CDC1551, IL-17 is required for early protective immunity against Mtb HN878 infection. The dependence on IL-17 to drive protective immunity against Mtb HN878 is due to the differential ability to induce high levels of IL-1β through a TLR-2-dependent mechanism, driving potent IL-17 responses, induction of the chemokine CXCL-13 and localization of T cells within lung lymphoid follicles for maximal macrophage activation and Mtb control. Together, our data change the existing paradigm that IL-17 is dispensable for primary immunity against Mtb infection, and suggests a differential requirement for IL-17 in protective immunity against some emerging Mtb strains.


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Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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PLOS Pathogens


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