Platelets Restrict the Oxidative Burst in Phagocytes and Facilitate Primary Progressive Tuberculosis

Rationale: Platelets are generated in the capillaries of the lung, control hemostasis and display immunological functions. Tuberculosis primarily affects the lung and patients show platelet changes and hemoptysis. A role of platelets in immunopathology of pulmonary tuberculosis requires careful assessment. Objectives: To identify the dynamics and interaction partners of platelets in the respiratory tissue and establish their impact on the outcome of pulmonary tuberculosis. Methods: Investigations were primarily performed in murine models of primary progressive pulmonary tuberculosis, by analysis of mouse strains with variable susceptibility to Mycobacterium tuberculosis infection, by platelet depletion and delivery of antiplatelet drugs. Measurements and Main Results: Platelets were present at the site of infection and formed aggregates with different myeloid subsets during experimental tuberculosis. Such aggregates were also detected in tuberculosis patients. Platelets were detrimental during the early phase of infection and this effect was uncoupled from their canonical activation. Platelets left lung cell dynamics and patterns of anti-mycobacterial T cell responses unchanged, but hampered antimicrobial defense by restricting production of reactive oxygen species in lung residing myeloid cells. Conclusion: Platelets are detrimental in primary progressive pulmonary tuberculosis, orchestrate lung immunity by modulating innate immune responsiveness and may be amenable to new interventions for this deadly disease.