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)-1β, 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 IFNƴ and TNFα.