Dunlap, C. | Search bioRxiv

bioRxiv2023

C5aR Expression in Kidney Tubules, Macrophages and Fibrosis

The anaphylatoxin C5a and its receptor C5aR (CD88) are complement pathway effectors implicated in renal diseases, including ANCA-associated vasculitis. We investigated the kidney expression of C5aR and a second C5a receptor C5L2 by using immunohistochemistry and in situ hybridization on formalin-fixed, paraffin-embedded human and mouse kidney. C5aR was detected on interstitial macrophages and in multiple tubular regions, both distal and proximal; C5L2 had a similar expression pattern. The 5/6 nephrectomy model of chronic kidney injury exhibited increased C5aR expression by infiltrating cells within the fibrotic regions. Functional assessment of myeloid C5aR in vitro revealed that C5a induced the expression of chemokines and remodeling factors by macrophages, including CCL-3/-4/-7,-20, MMP-1/-3/-8/-12, and F3, and promoted survival by blocking neutrophil apoptosis. C5a activity was C5aR dependent, as demonstrated by reversal with the C5aR inhibitor avacopan. Collectively, these results suggest that myeloid C5aR may induce excessive inflammation in the kidney via immune cell recruitment, extracellular matrix destruction, and remodeling, resulting in fibrotic tissue deposition.

immunology↗

bioRxiv2020

Culex pipiens L. and Culex restuans egg rafts harbor diverse bacterial communities compared to their midgut tissues

BackgroundThe bacterial communities associated with mosquito eggs are an essential component of the mosquito microbiota, yet there are few studies characterizing and comparing the microbiota of mosquito eggs to other host tissues. MethodsWe sampled gravid female Culex pipiens and Culex restuans from the field, allowed them to oviposit in the laboratory, and characterized the microbiota associated with their egg rafts and midguts for comparison through MiSeq sequencing of the 16S rRNA gene. ResultsBacterial richness was higher in egg rafts than in midguts for both species, and higher in Cx pipiens L. than Cx. restuans. The midgut samples of Cx. pipiens and Cx. restuans were dominated by Providencia. Culex pipiens L. and Cx. restuans egg rafts samples were dominated by Ralstonia and Novosphingobium, respectively. NMDS ordination based on Bray-Curtis distance matrix revealed that egg raft samples, or midgut tissues harbored similar bacterial communities regardless of the mosquito species. Within each mosquito species, there were distinct clustering of bacterial communities between egg raft and midgut tissues. ConclusionThese findings expand the list of described bacterial communities associated with Cx. pipiens L. and Cx. restuans and the additional characterization of the egg raft bacterial communities facilitates comparative analysis of mosquito host tissues, providing a basis for future studies seeking to understand any functional role of microbiota in mosquito biology.

microbiology↗