The Acute Phase of Chikungunya Virus Infection in Humans Is Associated With Strong Innate Immunity and T CD8 Cell Activation

Background. Rapidly spreading to new regions, including the islands of the Indian Ocean, Central Africa, and Europe, Chikungunya fever is becoming a major problem of public health. Unlike other members of the alphavirus genus, immune responses to Chikungunya virus (CHIKV) have been poorly investigated. Methods. We conducted a large ex vivo multiplex study of 50 cytokine, chemokine, and growth factor plasma profiles in 69 acutely infected patients from the Gabonese outbreak of 2007. We also assessed a phenotypic study of T lymphocyte responses during human acute CHIKV infection. Results. CHIKV infection in humans elicited strong innate immunity involving the production of numerous proinflammatory mediators. Interestingly, high levels of Interferon (IFN) alpha were consistently found. Production of interleukin (IL) 4, IL-10, and IFN-gamma suggested the engagement of the adaptive immunity. This was confirmed by flow cytometry of circulating T lymphocytes that showed a CD8+ T lymphocyte response in the early stages of the disease, and a CD4+ T lymphocyte mediated response in the later stages. For the first time to our knowledge, we found evidence of CD95-mediated apoptosis of CD4+ T lymphocytes during the first 2 days after symptoms onset, ex vivo. Conclusions. Together, our findings suggest that strong innate immunity is required to control CHIKV infection.