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 using 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 patients with tuberculosis. 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 antimycobacterial T-cell responses unchanged but hampered antimicrobial defense by restricting production of reactive oxygen species in lung-residing myeloid cells.

Conclusions

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.