Cytokine Responses to Plasmodium falciparum Liver-Stage Antigen 1 Vary in Rainy and Dry Seasons in Highland Kenya

Abstract

ABSTRACT Seasonal epidemics of malaria occur in highland areas of western Kenya where transmission intensity varies according to rainfall. This study describes the seasonal changes in cytokine responses to Plasmodium falciparum liver-stage antigen 1 (LSA-1) by children (≤17 years old) and adults (≥18 years old) living in such a highland area. Fourteen- to 24-mer peptides corresponding to the N- and C-terminal nonrepeat regions of LSA-1 stimulated production of interleukin-5 (IL-5), interleukin-10 (IL-10), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α) by peripheral blood mononuclear cells (PBMC) from 17 to 73% of individuals in both age groups in both seasons. IL-10 and TNF-α responses were more frequent during the high-transmission, rainy season than during the low-transmission, dry season (73 and 67% versus 17 and 25% response rates, respectively). In contrast, there was no seasonal change in the proportion of LSA-1-driven IFN-γ and IL-5 responses. Children produced less IFN-γ than adults, but IL-5, IL-10, and TNF-α levels were similar for both age groups. Depletion of CD8 + cells from PBMC decreased IFN-γ but increased IL-10 production. Individuals with LSA-1-stimulated IL-10 responses in the dry season were less likely to become reinfected in the subsequent rainy season than those without IL-10 responses (25% versus 49%; P = 0.083). These data support the notion that maintenance of LSA-1-driven IL-10 and TNF-α responses requires repeated and sustained exposure to liver-stage P. falciparum . In contrast, IFN-γ responses increase slowly with age but persist once acquired. CD8 + T cells are the major source of IFN-γ but may suppress production or secretion of IL-10.