Platelet-monocyte interaction in Mycobacterium tuberculosis infection.

ABSTRACT

The immune effects of platelets and platelet-leukocyte aggregation are increasingly recognized. We studied the occurrence of platelet-monocyte aggregation (PMA) in patients with pulmonary tuberculosis (TB), the processes underlying PMA and consequences for cytokine responses. In a cross-sectional study involving 65 Tanzanian TB patients in different phases of treatment and 29 healthy controls, TB patients had a significantly higher PMA. This increased PMA in TB patients was associated with increased monocyte CCR5, CD16 expression and PF4, but not with increased membrane-expressed or soluble P-selectin expression. These findings were confirmed in vitro whereas incubation of whole blood with Mycobacterium tuberculosis (Mtb) did not activate platelets, monocytes became activated with higher CD11b, CD16 and CCR5 expression, but this was independent of platelet-monocyte interaction. Still, platelets had an anti-inflammatory effect on cytokine responses as peripheral blood mononuclear cells (PBMC) incubated with Mtb in the presence of platelets produced less interleukin (IL)-1ß, tumor necrosis factor-α, IL-6 and interferon-γ and more IL-10. In conclusion, increased PMA during TB infection is caused by monocyte and not platelet activation. By counteracting the Mtb-induced pro-inflammatory leukocyte response, platelets may protect against excessive tissue damage, but may also compromise the production of protective cytokines, such as IFNÆ´ and TNFα.