Gut microbiota is essential in PGRP-LA regulated immune protection against Plasmodium berghei infection

Li Gao,Jingwen Wang,Xiumei Song

doi:10.1186/s13071-019-3876-y

Abstract

BackgroundMalaria remains to be one of the deadliest infectious diseases and imposes substantial financial and social costs in the world. Mosquitoes rely on the immune system to control parasite infection. Peptidoglycan recognition proteins (PGRPs), a family of pattern-recognition receptors (PRR), are responsible for initiating and regulating immune signaling pathways. PGRP-LA is involved in the regulation of immune defense against the Plasmodium parasite, however, the underlying mechanism needs to be further elucidated.MethodsThe spatial and temporal expression patterns of pgrp-la in Anopheles stephensi were analyzed by qPCR. The function of PGRP-LA was examined using a dsRNA-based RNA interference strategy. Western blot and periodic acid schiff (PAS) staining were used to assess the structural integrity of peritrophic matrix (PM).ResultsThe expression of pgrp-la in An. stephensi was induced in the midgut in response to the rapid proliferating gut microbiota post-blood meal. Knocking down of pgrp-la led to the downregulation of immune effectors that control gut microbiota growth. The decreased expression of these immune genes also facilitated P. berghei infection. However, such dsLA treatment did not influence the structural integrity of PM. When gut microbiota was removed by antibiotic treatment, the regulation of PGRP-LA on immune effectors was abolished and the knock down of pgrp-la failed to increase susceptibility of mosquitoes to parasite infection.ConclusionsPGRP-LA regulates the immune responses by sensing the dynamics of gut microbiota. A mutual interaction between gut microbiota and PGRP-LA contributes to the immune defense against Plasmodium parasites in An. stephensi.

Highlights

Malaria remains to be one of the deadliest infectious diseases and imposes substantial financial and social costs in the world
Because blood-feeding causes an extreme bloom of gut microbiota [9], we hypothesized that upregulation of pgrp-la in response to a blood meal could be due to the proliferation of gut microbiota
These results indicate that the induction of pgrp-la expression in response to blood-feeding, is a result of the proliferation of gut microbiota in the midgut

Summary

Introduction

Malaria remains to be one of the deadliest infectious diseases and imposes substantial financial and social costs in the world. Mosquitoes rely on the immune system to control parasite infection. A mosquito-borne disease (MBD), is caused by parasites of the genus Plasmodium. It remains to be a high concern of the World Health Organization due to the continued emergence and spread of drugresistant parasites and insecticide-resistant mosquitoes [1]. The main bottleneck for Plasmodium infection in the mosquito is the traverse of ookinetes across the midgut [3, 4]. During this process, two physical barriers are encountered by Plasmodium. PM poses an indispensable role in the defense of Plasmodium because its

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