microRNAs Involved in the Control of Innate Immunity in Candida Infected Caenorhabditis elegans

Abstract

The role of microRNAs (miRNAs) in regulating innate immune response to Candida albicans infection in Caenorhabditis elegans is still largely unclear. Using small RNA SOLiD deep sequencing technique, we profiled the miRNAs that were dysregulated by C. albicans infection. We identified 16 miRNAs that were up-regulated and 4 miRNAs that were down-regulated in nematodes infected with C. albicans. Bioinformatics analysis implied that these dysregulated miRNAs may be involved in the control of many important biological processes. Using available mutants, we observed that mir-251 and mir-252 loss-of-function mutants were resistant to C. albicans infection, whereas mir-360 mutants were hypersensitive to C. albicans infection. The expression pattern of antimicrobial genes suggested that mir-251, mir-252, and mir-360 played crucial roles in regulating the innate immune response to C. albicans infection. Fungal burden might be closely associated with altered lifespan and innate immune response in mir-251, mir-252, and mir-360 mutants. Moreover, mir-251 and mir-252 might function downstream of p38 mitogen activated protein kinase (MAPK) or IGF-1/insulin-like pathway to regulate the innate immune response to C. albicans infection. Our results provide an important molecular basis for further elucidating how miRNA-mRNA networks may control the innate immune response to C. albicans infection.

miRNA activity contributes to accurate RNA splicing inC. elegansintestine and body muscle tissues

“…These three genes act together to produce a transcriptional innate immune response where the transcription factor atf-7 is activated through phosphorylation by kinases pmk-1 and sek-1 . Consistent with our findings, the role of miRNAs in regulating the innate immune response through the intestine and these genes has been reported in multiple studies (Ding et al 2008; Kudlow et al 2012; Sun et al 2016).…”

mir-355 Functions as An Important Link between p38 MAPK Signaling and Insulin Signaling in the Regulation of Innate Immunity

“…Under normal conditions, loss-of-function mutation of mir-45 , mir-63 , mir-75 , mir-246 , mir-256 , or mir-355 did not obviously affect the longevity (data not shown). Under normal conditions, loss-of-function mutation of mir-360 also does not affect the longevity 21 .…”

“…Some important and conserved signaling pathways, including p38 mitogen-activated protein kinase (MAPK), insulin, and TGF-β signaling pathways, have been identified to be required for the control of innate immunity in C. elegans 15 – 17 . Recently, some miRNAs, such as let-7, mir-84 , mir-241 , mir-251 , mir-252 , and mir-2 33, have been further shown to be involved in the control of innate immune response to pathogen infection in C. elegans 18 – 21 . Nevertheless, the potential involvement of most of miRNAs in the control of innate immunity is still unknown in C. elegans .…”

Tobacco Hornworm (Manduca sexta) caterpillars as a novel host model for the study of fungal virulence and drug efficacy

“…This new model system allows for fungal burden to be monitored throughout the course of infection in a single animal via CFU count. This is unlike any other experimental system, where fungal burden is either an endpoint measure in the mouse kidney, in homogenised was moth larvae 49 ,nematodes 50 , flies 51 , or requires genetically modified fluorescent yeast strains for microscopic imaging and analyses 52 . While we did detect very low CFU counts in the PBS control 3 days post infection, we consider this spurious finding due to cross contamination as preliminary experiments of plating contents of hemolymph and faeces of naïve animals did not detect any yeast growth (data not shown).…”