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Mosquito C-type lectins maintain gut microbiome homeostasis

Abstract

The long-term evolutionary interaction between the host immune system and symbiotic bacteria determines their cooperative rather than antagonistic relationship. It is known that commensal bacteria have evolved a number of mechanisms to manipulate the mammalian host immune system and maintain homeostasis. However, the strategies employed by the microbiome to overcome host immune responses in invertebrates still remain to be understood. Here, we report that the gut microbiome in mosquitoes utilizes C-type lectins (mosGCTLs) to evade the bactericidal capacity of antimicrobial peptides (AMPs). Aedes aegypti mosGCTLs facilitate colonization by multiple bacterial strains. Furthermore, maintenance of the gut microbial flora relies on the expression of mosGCTLs in A. aegypti. Silencing the orthologues of mosGCTL in another major mosquito vector (Culex pipiens pallens) also impairs the survival of gut commensal bacteria. The gut microbiome stimulates the expression of mosGCTLs, which coat the bacterial surface and counteract AMP activity. Our study describes a mechanism by which the insect symbiotic microbiome offsets gut immunity to achieve homeostasis.

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Figure 1: The role of mosGCTLs in systemic bacterial inoculation in A. aegypti.
Figure 2: mosGCTLs facilitate the colonization of the A. aegypti midgut by gut bacteria.
Figure 3: mosGCTLs contribute to the maintenance of gut microbiota in A. aegypti and C. pipiens pallens.
Figure 4: mosGCTLs and AMPs are simultaneously regulated by the Imd pathway.
Figure 5: mosGCTLs are antagonists for AMP-mediated bacterial elimination.
Figure 6: mosGCTLs interrupt the deposition of AMPs onto bacteria cells.

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Acknowledgements

This work was funded by grants from the National Natural Science Foundation of China (81301412, 81422028, 81571975 and 61472205), the National Key Basic Research Program of the Chinese Ministry of Science and Technology (MOST) (2013CB911500), the Excellent Young Scientist Foundation of Beijing (2013D009004000002), Grand Challenges Explorations of the Bill & Melinda Gates Foundation (OPP1021992), and the National Institute of Health of the United States (AI103807 and AI099625). We thank the Professor George K. Christophides from Imperial College London, who provided critical suggestions for the manuscript. G.C. is a Newton Advanced Fellow awarded by the Academy of Medical Sciences and the Newton Fund, and a Janssen Investigator of Tsinghua University. We thank the technical supports from the Core Facility of Center for Life Sciences and Center of Biomedical Analysis (Tsinghua University).

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G.C. designed the experiments and wrote the manuscript; X.P. performed the majority of the experiments and analysed data; X.X., R.Z., Y. L. and J.L. helped with the RNA isolation and qPCR detection; Q.L. provided Culex pipiens pallens and contributed to the discussion. P.W. contributed experimental suggestions and strengthened the writing of the manuscript. All authors reviewed, critiqued and provided comments to the text.

Corresponding author

Correspondence to Gong Cheng.

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Pang, X., Xiao, X., Liu, Y. et al. Mosquito C-type lectins maintain gut microbiome homeostasis. Nat Microbiol 1, 16023 (2016). https://doi.org/10.1038/nmicrobiol.2016.23

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