Platelet function in HIV plus dengue coinfection associates with reduced inflammation and milder dengue illness

Abstract

HIV-infected subjects under virological control still exhibit a persistent proinflammatory state. Thus, chronic HIV infection changes the host homeostasis towards an adapted immune response that may affect the outcome of coinfections. However, little is known about the impact of HIV infection on inflammatory amplification and clinical presentation in dengue. Platelets have been shown to participate in immune response in dengue and HIV. We hypothesized that altered platelet responses in HIV-infected subjects may contribute to altered inflammatory milieu and disease progression in dengue. We prospectively followed a cohort of 84 DENV-infected patients of whom 29 were coinfected with HIV under virological control. We report that dengue and HIV coinfection progress with reduced inflammation and milder disease progression with lower risk of vascular instability. Even though the degree of thrombocytopenia and platelet activation were similar between dengue-infected and HIV plus dengue-coinfected patients, plasma levels of the platelet-derived chemokines RANTES/CCL5 and PF4/CXCL4 were lower in coinfection. Consistently, platelets from coinfected patients presented defective secretion of the stored-chemokines PF4 and RANTES, but not newly synthesized IL-1β, when cultured ex vivo . These data indicate that platelets from HIV-infected subjects release lower levels of chemokines during dengue illness, which may contribute to milder clinical presentation during coinfection.

Platelet activation and platelet-monocyte aggregate formation trigger tissue factor expression in patients with severe COVID-19

“… 14 , 22 , 27 , 28 Our group and others have previously shown that platelet activation and platelet-leukocyte interactions participate in the pathophysiology of viral infections, including dengue, HIV, and influenza. 20 , 29 - 35 Our central hypothesis is that platelet activation and platelet-monocyte aggregate formation participate in thromboinflammatory responses during COVID-19.…”

Apoptosis characterization in mononuclear blood leukocytes of HIV patients during dengue acute disease

“…In agreement with our study, Fas/CD95 expression on T cells were not significantly different in patients receiving ART and degree of Fas/CD95-expressing lymphocytes was comparable between GBV-C co-infected and GBV-C infected 39 . A recent study demonstrated that apoptosis of platelets were similar between DENV infected and coinfected with HIV as evidenced by phosphatidylserine exposure, mitochondrial membrane potential and caspase -9 activation 26 .…”

“…Corroborating, the present data demonstrated that most coinfected patients had mild symptons confirming our previous data 14 . More recently, Hotzz et.al., reported that DENV infection in ART-treated HIV patients was associated with reduced vascular instability and liver damage 26 . However, coinfected patients could have severe dengue outcomes 27 .…”

Innate immune receptors in platelets and platelet-leukocyte interactions

“…4A). Of note, increased platelet activation with the exhaustion of α‐granule chemokines is associated with high viral load and immune suppression in AIDS patients, 263 and persists in HIV‐infected subjects under virologic control 264,265 …”

“…Of note, increased platelet activation with the exhaustion of -granule chemokines is associated with high viral load and immune suppression in AIDS patients, 263 and persists in HIV-infected subjects under virologic control. 264,265 Increased levels of platelet-derived sCD40L participate in HIVassociated neuroinflammation by inducing platelet-monocyte aggregation and infiltration through the blood-brain barrier (Fig. 4A).…”