Pulmonary Infection with Hypervirulent Mycobacteria Reveals a Crucial Role for the P2X7 Receptor in Aggressive Forms of Tuberculosis

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Nearly 9 million new cases of tuberculosis and 1.3 million deaths are reported yearly worldwide. Most individuals infected with tubercle bacilli remain asymptomatic; however, some develop active tuberculosis due to the reactivation of latent infections. Progressive primary tuberculosis is an alternative form of the disease that mostly affects children and immunocompromised individuals. Extensive pneumonia, pulmonary necrosis and bacillus dissemination characterize some of the aggressive forms of tuberculosis. To investigate the molecular mechanisms that underlie severe disease progression, we used experimental models of relatively resistant C57BL/6 mice that were infected with highly virulent strains of Mycobacterium tuberculosis or Mycobacterium bovis. Two hypervirulent strains (Mtb strain 1471 and Mbv strain MP287/03) induced extensive pulmonary inflammation and necrosis in mice and promoted bacillus dissemination and animal death. We hypothesized that the innate immune response to endogenous damage signals from necrotic cells could aggravate the disease. We focused our study on the purinergic P2X7 receptor (P2X7R), a sensor of ATP that is released from necrotic cells and that induces pro-inflammatory cytokine production and cell death. Our data provide new insights into the pathogenesis of severe tuberculosis by showing that mice that lack P2X7R have attenuated disease with substantially reduced bacillus dissemination and lung inflammation without evidence of necrosis.

Vyšlo v časopise: Pulmonary Infection with Hypervirulent Mycobacteria Reveals a Crucial Role for the P2X7 Receptor in Aggressive Forms of Tuberculosis. PLoS Pathog 10(7): e32767. doi:10.1371/journal.ppat.1004188
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004188

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