期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：26
页码：E3412-E3420
DOI：10.1073/pnas.1420078112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceThe innate immune response is a major determinant of malaria parasite success in its mosquito host. Previous experiments have implicated LPS-induced TNF transcription factor (LITAF)-like 3 (LL3) as an integral component of the mosquito immune response to the malaria parasite. This study reports that LL3 influences oocyst survival and demonstrates its role in mosquito blood cell (hemocyte) differentiation in response to parasite infection. Integrating previous data, we provide evidence that hemocytes are critical modulators of the mosquito late-phase immune response. Our findings provide new insight into how parasites are killed in the mosquito host and define major roles for LL3 and the STAT pathways in Plasmodium oocyst survival. Plasmodium parasites must complete development in the mosquito vector for transmission to occur. The mosquito innate immune response is remarkably efficient in limiting parasite numbers. Previous work has identified a LPS-induced TNF transcription factor (LITAF)-like transcription factor, LITAF-like 3 (LL3), which significantly influences parasite numbers. Here, we demonstrate that LL3 does not influence invasion of the mosquito midgut epithelium or ookinete-to-oocyst differentiation but mediates a late-phase immune response that decreases oocyst survival. LL3 expression in the midgut and hemocytes is activated by ookinete midgut invasion and is independent of the mosquito microbiota, suggesting that LL3 may be a component of a wound-healing response. LL3 silencing abrogates the ability of mosquito hemocytes to differentiate and respond to parasite infection, implicating hemocytes as critical modulators of the late-phase immune response.
