Infectious status of sporozoites evoke Innate response, leading to Cell-mediated protective CD8+T cell response against Plasmodia infection

Abstract

SUMMARY: The initial host innate response against the pathogen might dictate the protective memory response, and encompasses an array of innate immune mediators. The infectious status of sporozoite plays an instrumental role in liver stage immunity and impact the host innate response, which leads to CD8+T cell response in rendering sterile-protection. Innate recognition of infection in vertebrates can lead to the induction of adaptive immune responses through activation of innate immune cells especially dendritic cells (DCs). DCs are activated directly by conserved pathogen molecules and indirectly by inflammatory mediators produced by other innate cell types that recognize such molecules. The DCs are an indispensable component of priming and generation of CD8+T cell responses. As CD8+T cells are the major effector cell populations which extends protective immunity against liver-stage infection. Present study shows that innate immune response induced by infectious sporozoites challenge is qualitatively different, and helps rescue the loss of CD8+T cell response as has been observed in γ-spz immunization without intermittent challenge. The danger signals perceived from the pathogen attack are decisive in establishing the nature of innate immune response, leading to long-term protection. In our results, accumulation of CD8α+ DCs is significantly higher in the case of infectious immunized group as compare to RAS as well as sham immunized group. The higher expression of MHC II, CD80, CD86 and CD40 molecules on the surface of CD8α+ DCs represents the activation status of CD8α+ DCs, reflecting the role of infectious sporozoites in modulating the T cell immune response. Subsequently, cytokine expression studies in kinetic and independent manner and found that up-regulation of various cytokines i.e. IL-15, IFN-γ, TNF-α, IL-10 and Type I interferon in response to infectious sporozoites immunization. While from this study we also found that the expression of IL-10 got saturated at 72 hrs. By the cytokine study we tried to understand the innate immune mediator’s and we would like to have some idea about the PAMPs involved in innate immunity as they are the key to adaptive immune response.