{
"@context": "http://schema.org",
"@type": "ScholarlyArticle",
"@id": "https://doi.org/10.6084/m9.figshare.17156681.v1",
"url": "https://tandf.figshare.com/articles/journal_contribution/_i_M_tuberculosis_i_CRISPR_Cas_proteins_are_secreted_virulence_factors_that_trigger_cellular_immune_responses/17156681/1",
"additionalType": "Journal contribution",
"name": "M. tuberculosis CRISPR/Cas proteins are secreted virulence factors that trigger cellular immune responses",
"author": [
{
"name": "Jianjian Jiao",
"givenName": "Jianjian",
"familyName": "Jiao"
},
{
"name": "Nan Zheng",
"givenName": "Nan",
"familyName": "Zheng"
},
{
"name": "Wenjing Wei",
"givenName": "Wenjing",
"familyName": "Wei"
},
{
"name": "Joy Fleming",
"givenName": "Joy",
"familyName": "Fleming"
},
{
"name": "Xingyun Wang",
"givenName": "Xingyun",
"familyName": "Wang"
},
{
"name": "Zihui Li",
"givenName": "Zihui",
"familyName": "Li"
},
{
"name": "Lili Zhang",
"givenName": "Lili",
"familyName": "Zhang"
},
{
"name": "Yi Liu",
"givenName": "Yi",
"familyName": "Liu"
},
{
"name": "Zongde Zhang",
"givenName": "Zongde",
"familyName": "Zhang"
},
{
"name": "Adong Shen",
"givenName": "Adong",
"familyName": "Shen"
},
{
"name": "Li Chuanyou",
"givenName": "Li",
"familyName": "Chuanyou"
},
{
"name": "Lijun Bi",
"givenName": "Lijun",
"familyName": "Bi"
},
{
"name": "Hongtai Zhang",
"givenName": "Hongtai",
"familyName": "Zhang"
}
],
"description": "The role of prokaryotic CRISPR/Cas system proteins as a defensive shield against invasive nucleic acids has been studied extensively. Non-canonical roles in pathogenesis involving intracellular targeting of certain virulence-associated endogenous mRNA have also been reported for some Type I and Type II CRISPR/Cas proteins, but no such roles have yet been established for Type III system proteins. Here, we demonstrate that M. tuberculosis (Type III-A system) CRISPR/Cas proteins Csm1, Csm3, Csm5, Csm6, and Cas6 are secreted and induce host immune responses. Using cell and animal experiments, we show that Cas6, in particular, provokes IFN-γ release from PBMCs from active tuberculosis (TB) patients, and its deletion markedly attenuates virulence in a murine M. tuberculosis challenge model. Recombinant MTBCas6 induces apoptosis of macrophages and lung fibroblasts, and interacts with the surface of cells in a caspase and TLR-2 independent manner. Transcriptomic and signal pathway studies using THP-1 macrophages stimulated with MTBCas6 indicated that MTBCas6 upregulates expression of genes associated with the NF-κB pathway leading to higher levels of IL-6, IL-1β, and TNF-α release, cytokines known to activate immune system cells in response to M. tuberculosis infection. Our findings suggest that, in addition to their intracellular shielding role, M. tuberculosis CRISPR/Cas proteins have non-canonical extracellular roles, functioning like a virulent sword, and activating host immune responses.",
"license": "https://creativecommons.org/licenses/by/4.0/legalcode",
"keywords": "Microbiology, FOS: Biological sciences, Cell Biology, Genetics, Molecular Biology, Science Policy, Immunology, FOS: Clinical medicine, Biological Sciences not elsewhere classified, Cancer, Infectious Diseases, FOS: Health sciences, Computational Biology",
"contentSize": "1141918 Bytes",
"dateCreated": "2021-12-10",
"datePublished": "2021",
"dateModified": "2024-03-21",
"sameAs": {
"@id": "https://doi.org/10.6084/m9.figshare.17156681",
"@type": "CreativeWork"
},
"@reverse": {
"isBasedOn": {
"@id": "https://doi.org/10.1080/21505594.2021.2007621",
"@type": "ScholarlyArticle"
}
},
"schemaVersion": "http://datacite.org/schema/kernel-4",
"publisher": {
"@type": "Organization",
"name": "Taylor & Francis"
},
"provider": {
"@type": "Organization",
"name": "datacite"
}
}