Asymptomatic vivax malaria is associated with an IFN-γ-program on adaptive immunity

The adaptive immunity against Plasmodium vivax is thought to be essential to limit parasite growth during asymptomatic malaria, preventing the occurrence of symptoms. However, the mechanisms governing clinical immunity during asymptomatic infections are not understood. Here, we investigated the adaptive cellular compartment in asymptomatic P. vivax-infected individuals (ASY) compared to symptomatic patients (SY) and healthy donors (CTL). Our integrative analysis revealed a T_H1-biased immune signature with expanded populations of T_H1 CD4⁺ T cells associated with the asymptomatic infection. In addition, there is an expanded population of proliferating atypical memory B cells that correlate with IgG levels against P. vivax antigens and parasitemia. The absence of systemic inflammation based on a comprehensive panel of soluble markers and the lower expression of some regulatory markers suggests a controlled inflammatory response that can be derived from an effective control of parasite growth. Our findings suggest that ASY maintain a pool of IFN-γ-associated Th cell phenotypes that orchestrate the immune response, limiting parasitemia and preventing clinical malaria.