Cellular Microbiology最新文献

{"title":"Inflammasome activation and IL-1β signalling in group A Streptococcus disease","authors":"Johanna Richter,&nbsp;Stephan Brouwer,&nbsp;Kate Schroder,&nbsp;Mark J. Walker","doi":"10.1111/cmi.13373","DOIUrl":"10.1111/cmi.13373","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Group A <i>Streptococcus</i> (GAS) is a Gram-positive bacterial pathogen that causes significant morbidity and mortality worldwide. Recent clinical evidence suggests that the inflammatory marker interleukin-1β (IL-1β) plays an important role in GAS disease progression, and presents a potential target for therapeutic intervention. Interaction with GAS activates the host inflammasome pathway to stimulate production and secretion of IL-1β, but GAS can also stimulate IL-1β production in an inflammasome-independent manner. This review highlights progress that has been made in understanding the importance of host cell inflammasomes and IL-1 signalling in GAS disease, and explores challenges and unsolved problems in this host-pathogen interaction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Take Away</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Inflammasome signalling during GAS infection is an emerging field of research.</li>\u0000 \u0000 <li>GAS modulates the NLRP3 inflammasome pathway through multiple mechanisms.</li>\u0000 \u0000 <li>SpeB contributes to IL-1β production independently of the inflammasome pathway.</li>\u0000 \u0000 <li>IL-1β signalling can be host-protective, but also drive severe GAS disease.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 9","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13373","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39095839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A putative PKA phosphorylation site S227 in MoSom1 is essential for infection-related morphogenesis and pathogenicity in Magnaporthe oryzae","authors":"Shuzhen Deng,&nbsp;Lin Xu,&nbsp;Zhe Xu,&nbsp;Wuyun Lv,&nbsp;Zhengxian Chen,&nbsp;Nan Yang,&nbsp;Nicholas J. Talbot,&nbsp;Zhengyi Wang","doi":"10.1111/cmi.13370","DOIUrl":"10.1111/cmi.13370","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>In the rice blast fungus <i>Magnaporthe oryzae</i>, the cAMP signalling pathway plays a critical role in regulating leaf surface recognition and the initiation of appressorium development. Direct downstream targets of the cAMP signalling pathway are, however, not well-characterised. The MoSom1 protein functions downstream of the cAMP dependent protein kinase A (cAMP-PKA) and is essential for infection-related morphogenesis and pathogenicity. In this study, we show that mutation of a putative PKA phosphorylation site in MoSom1 is essential for its role in appressorium differentiation and pathogenicity in <i>M. oryzae</i>. Mutation of serine 227 in MoSom1 by deletion or serine (S) substitution to alanine (A), valine (V) or tyrosine (Y), resulted in defects of conidiation, appressorium-like structure formation and fungal pathogenicity. Western blot analysis confirmed that S227 in MoSom1 is a putative PKA phosphorylation site. Furthermore, a <i>ΔMosom1</i> mutant showed reduced expression of <i>PMK1</i> and was defective in Pmk1 phosphorylation, indicating that the Pmk1 mitogen-activated protein kinase (MAPK) acts downstream of MoSom1 in <i>M. oryzae</i>. We conclude that the cAMP-PKA pathway may regulate the Pmk1 MAPK pathway through MoSom1 during rice infection by the blast fungus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Take Aways</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>S227 is crucial for MoSom1 function in <i>M. oryzae</i>.</li>\u0000 \u0000 <li>S227 in MoSom1 was identified as a putative PKA phosphorylation site in <i>M. oryzae</i>.</li>\u0000 \u0000 <li>S227 is essential for infection-related morphogenesis and pathogenicity in <i>M. oryzae</i>.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13370","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39064388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Candidalysin triggers epithelial cellular stresses that induce necrotic death","authors":"Mariana Blagojevic,&nbsp;Giorgio Camilli,&nbsp;Michelle Maxson,&nbsp;Bernhard Hube,&nbsp;David L. Moyes,&nbsp;Jonathan P. Richardson,&nbsp;Julian R. Naglik","doi":"10.1111/cmi.13371","DOIUrl":"10.1111/cmi.13371","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p><i>Candida albicans</i> is a common opportunistic fungal pathogen that causes a wide range of infections from superficial mucosal to hematogenously disseminated candidiasis. The hyphal form plays an important role in the pathogenic process by invading epithelial cells and causing tissue damage. Notably, the secretion of the hyphal toxin candidalysin is essential for both epithelial cell damage and activation of mucosal immune responses. However, the mechanism of candidalysin-induced cell death remains unclear. Here, we examined the induction of cell death by candidalysin in oral epithelial cells. Fluorescent imaging using healthy/apoptotic/necrotic cell markers revealed that candidalysin causes a rapid and marked increase in the population of necrotic rather than apoptotic cells in a concentration dependent manner. Activation of a necrosis-like pathway was confirmed since <i>C. albicans</i> and candidalysin failed to activate caspase-8 and -3, or the cleavage of poly (ADP-ribose) polymerase. Furthermore, oral epithelial cells treated with candidalysin showed rapid production of reactive oxygen species, disruption of mitochondria activity and mitochondrial membrane potential, ATP depletion and cytochrome c release. Collectively, these data demonstrate that oral epithelial cells respond to the secreted fungal toxin candidalysin by triggering numerous cellular stress responses that induce necrotic death.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Take aways</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Candidalysin secreted from <i>Candida albicans</i> causes epithelial cell stress.</li>\u0000 \u0000 <li>Candidalysin induces calcium influx and oxidative stress in host cells.</li>\u0000 \u0000 <li>Candidalysin induces mitochondrial dysfunction, ATP depletion and epithelial necrosis.</li>\u0000 \u0000 <li>The toxicity of candidalysin is mediated from the epithelial cell surface.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13371","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39076404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide genetic screen identifies host ubiquitination as important for Legionella pneumophila Dot/Icm effector translocation","authors":"Sze Ying Ong,&nbsp;Ralf Schuelein,&nbsp;Rachelia R. Wibawa,&nbsp;Daniel W. Thomas,&nbsp;Yanny Handoko,&nbsp;Saskia Freytag,&nbsp;Melanie Bahlo,&nbsp;Kaylene J. Simpson,&nbsp;Elizabeth L. Hartland","doi":"10.1111/cmi.13368","DOIUrl":"10.1111/cmi.13368","url":null,"abstract":"<p>The Dot/Icm system of <i>Legionella pneumophila</i> is essential for virulence and delivers a large repertoire of effectors into infected host cells to create the <i>Legionella</i> containing vacuole. Since the secretion of effectors via the Dot/Icm system does not occur in the absence of host cells, we hypothesised that host factors actively participate in Dot/Icm effector translocation. Here we employed a high-throughput, genome-wide siRNA screen to systematically test the effect of silencing 18,120 human genes on translocation of the Dot/Icm effector, RalF, into HeLa cells. For the primary screen, we found that silencing of 119 genes led to increased translocation of RalF, while silencing of 321 genes resulted in decreased translocation. Following secondary screening, 70 genes were successfully validated as ‘high confidence’ targets. Gene set enrichment analysis of siRNAs leading to decreased RalF translocation, showed that ubiquitination was the most highly overrepresented category in the pathway analysis. We further showed that two host factors, the E2 ubiquitin-conjugating enzyme, UBE2E1, and the E3 ubiquitin ligase, CUL7, were important for supporting Dot/Icm translocation and <i>L. pneumophila</i> intracellular replication. In summary, we identified host ubiquitin pathways as important for the efficiency of Dot/Icm effector translocation by <i>L. pneumophila</i>, suggesting that host-derived ubiquitin-conjugating enzymes and ubiquitin ligases participate in the translocation of <i>Legionella</i> effector proteins and influence intracellular persistence and survival.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13368","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39023821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recombinant IL-22 promotes protection in a murine model of Aspergillus flavus keratitis and mediates host immune responses in human corneal epithelial cells","authors":"Lakshmi Sruthi Mallela,&nbsp;Prerana Sharma,&nbsp;Tata Santosh RamaBhadra Rao,&nbsp;Sanhita Roy","doi":"10.1111/cmi.13367","DOIUrl":"10.1111/cmi.13367","url":null,"abstract":"<p><i>Aspergillus flavus</i> is a leading cause of corneal infections in India and worldwide, resulting in severe visual impairment. We studied the host immune response towards <i>A. flavus</i> in immortalised human corneal epithelial cells (HCEC) and found increased expression of Toll-like receptors, antimicrobial peptides and proinflammatory cytokines like IL-6 and IL-8. Differential expressions of antimicrobial peptides were determined in corneal scrapings from <i>A. flavus</i> keratitis patients with significantly increased expression of LL-37, S100A12 and RNase 7. Increased levels of IL-22 expression were observed both in patients with <i>A. flavus</i> keratitis and in experimental mice model of corneal infections along with IL-17, IL-23 and IL-18. IL-22 is an important mediator of inflammation during microbial infections, and acts primarily on fibroblasts and epithelial cells. We observed constitutive expression of IL-22 receptors in HCEC, and IL-22 mediated activation of NF-κB, MAPK pathways and STAT3, along with increased expression of antimicrobial peptides in these cells. IL-22 also efficiently lessened cell deaths in corneal epithelial cells during <i>A. flavus</i> infection in vitro. Furthermore, recombinant IL-22 reduced fungal burden and corneal opacity in an experimental murine model of <i>A. flavus</i> keratitis.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 9","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13367","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39013774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The type III secretion system effector EspO of enterohaemorrhagic Escherichia coli inhibits apoptosis through an interaction with HAX-1","authors":"Sharanya Chatterjee,&nbsp;Sujinna Lekmeechai,&nbsp;Nicolas Constantinou,&nbsp;Ewa A. Grzybowska,&nbsp;Zuzanna Kozik,&nbsp;Jyoti S. Choudhary,&nbsp;Cedric N. Berger,&nbsp;Gad Frankel,&nbsp;Abigail Clements","doi":"10.1111/cmi.13366","DOIUrl":"10.1111/cmi.13366","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Many enteric pathogens employ a type III secretion system (T3SS) to translocate effector proteins directly into the host cell cytoplasm, where they subvert signalling pathways of the intestinal epithelium. Here, we report that the anti-apoptotic regulator HS1-associated protein X1 (HAX-1) is an interaction partner of the T3SS effectors EspO of enterohaemorrhagic <i>Escherichia coli</i> (EHEC) and <i>Citrobacter rodentium</i>, OspE of <i>Shigella flexneri</i> and Osp1_STYM of <i>Salmonella enterica</i> serovar Typhimurium. EspO, OspE and Osp1_STYM have previously been reported to interact with the focal adhesions protein integrin linked kinase (ILK). We found that EspO localizes both to the focal adhesions (ILK localisation) and mitochondria (HAX-1 localisation), and that increased expression of HAX-1 leads to enhanced mitochondrial localisation of EspO. Ectopic expression of EspO, OspE and Osp1_STYM protects cells from apoptosis induced by staurosporine and tunicamycin. Depleting cells of HAX-1 indicates that the anti-apoptotic activity of EspO is HAX-1 dependent. Both HAX-1 and ILK were further confirmed as EspO1-interacting proteins during infection using T3SS-delivered EspO1. Using cell detachment as a proxy for cell death we confirmed that T3SS-delivered EspO1 could inhibit cell death induced during EPEC infection, to a similar extent as the anti-apoptotic effector NleH, or treatment with the pan caspase inhibitor z-VAD. In contrast, in cells lacking HAX-1, EspO1 was no longer able to protect against cell detachment, while NleH1 and z-VAD maintained their protective activity. Therefore, during both infection and ectopic expression EspO protects cells from cell death by interacting with HAX-1. These results suggest that despite the differences between EHEC, <i>C</i>. <i>rodentium</i>, <i>Shigella</i> and <i>S</i>. <i>typhimurium</i> infections, hijacking HAX-1 anti-apoptotic signalling is a common strategy to maintain the viability of infected cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Take Away</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>EspO homologues are found in EHEC, <i>Shigella</i>, <i>S</i>. <i>typhimurium</i> and some EPEC.</li>\u0000 \u0000 <li>EspO homologues interact with HAX-1.</li>\u0000 \u0000 <li>EspO protects infected cells from apoptosis.</li>\u0000 \u0000 <li>EspO joins a growing list of T3SS effectors that manipulate cell death pathways.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 9","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13366","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39007994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Host lactosylceramide enhances Edwardsiella tarda infection","authors":"Kazuki Oishi,&nbsp;Moeri Morise,&nbsp;Linh Khanh Vo,&nbsp;Nhung Thi Tran,&nbsp;Daichi Sahashi,&nbsp;Rena Ueda-Wakamatsu,&nbsp;Wataru Nishimura,&nbsp;Masaharu Komatsu,&nbsp;Kazuhiro Shiozaki","doi":"10.1111/cmi.13365","DOIUrl":"10.1111/cmi.13365","url":null,"abstract":"<p><i>Edwardsiella tarda</i> is a Gram-negative bacterium causing economic damage in aquaculture. The interaction of <i>E. tarda</i> with microdomains is an important step in the invasion, but the target molecules in microdomains remain undefined. Here, we found that intraperitoneal injection of <i>E. tarda</i> altered splenic glycosphingolipid patterns in the model host medaka (<i>Oryzias latipes</i>) accompanied by alteration of glycosphingolipid metabolism-related gene expressions, suggesting that glycosphingolipid levels are involved in <i>E. tarda</i> infection. To ascertain the significance of glycosphingolipids in the infection, fish cell lines, DIT29 cells with a high amount of lactosylceramide (LacCer) and glucosylceramide (GlcCer), and GAKS cells with a low amount of these lipids, were treated with methyl-β-cyclodextrin to disrupt the microdomain. <i>E. tarda</i> infection was suppressed in DIT29 cells, but not in GAKS cells, suggesting the involvement of microdomain LacCer and GlcCer in the infection. DL-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol, an inhibitor of glycosphingolipid-synthesis, attenuated the infection in DIT29 cells, while Neu3-overexpressing GAKS cells, which accumulated LacCer, enhanced the infection. <i>E. tarda</i> possessed binding ability towards LacCer, but not GlcCer, and LacCer preincubation declined the infection towards fish cells, possibly due to the masking of binding sites. The present study suggests that LacCer may be a positive regulator of <i>E. tarda</i> invasion.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 9","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13365","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38982659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cover Image: Coxiella burnetii encodes an LvgA-related protein important for intracellular replication (Cellular Microbiology 06/2021)","authors":"Samuel Steiner,&nbsp;Amit Meir,&nbsp;Craig R. Roy","doi":"10.1111/cmi.13351","DOIUrl":"10.1111/cmi.13351","url":null,"abstract":"<p>Immunofluorescence micrograph of HeLa cells infected for 5 days with a <i>Coxiella burnetii cbu1754</i>::Tn mutant expressing cbu1754 in trans. DAPI (blue), <i>C. burnetii</i> (red), lysosome marker LAMP-1 (green). For further details, readers are referred to the article by Steiner et al. on p. e13331 of this issue.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13351","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47871262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type III secreted effectors that target mitochondria","authors":"Ipsita Nandi,&nbsp;Lior Aroeti,&nbsp;Rachana Pattani Ramachandran,&nbsp;Ephrem G. Kassa,&nbsp;Efrat Zlotkin-Rivkin,&nbsp;Benjamin Aroeti","doi":"10.1111/cmi.13352","DOIUrl":"10.1111/cmi.13352","url":null,"abstract":"<p>A type III secretion system (T3SS) is used by Gram-negative bacterial pathogens to secrete and translocate a battery of proteins, termed effectors, from the bacteria directly into the host cells. These effectors, which are thought to play a key role in bacterial virulence, hijack and modify the activity of diverse host cell organelles, including mitochondria. Mitochondria—the energy powerhouse of the cell—are important cell organelles that play role in numerous critical cellular processes, including the initiation of apoptosis and the induction of innate immunity. Therefore, it is not surprising that pathogenic bacteria use mitochondrially targeted effectors to control host cell death and immunity pathways. Surprisingly, however, we found that despite their importance, only a limited number of type III secreted effectors have been characterised to target host mitochondria, and the mechanisms underlying their mitochondrial activity have not been sufficiently analysed. These include effectors secreted by the enteric attaching and effacing (A/E), <i>Salmonella</i> and <i>Shigella</i> bacterial pathogens. Here we give an overview of key findings, present gaps in knowledge and hypotheses concerning the mode by which these type III secreted effectors control the host and the bacterial cell life (and death) through targeting mitochondria.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 9","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13352","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38968609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenesis of Borrelia burgdorferi and Babesia microti in TLR4-Competent and TLR4-dysfunctional C3H mice","authors":"Lavoisier Akoolo,&nbsp;Vitomir Djokic,&nbsp;Sandra C. Rocha,&nbsp;Nikhat Parveen","doi":"10.1111/cmi.13350","DOIUrl":"10.1111/cmi.13350","url":null,"abstract":"<p><i>Toll-like receptors</i> (TLRs) are a class of membrane-spanning <i>proteins of host cells</i>. TLR2 and TLR4 are displayed on the surface of macrophages, neutrophils and dendritic cells and recognise structurally conserved microbial signatures defined as Pathogen associated molecular patterns (PAMPs). C3H mice are susceptible to tick-borne pathogens; Lyme disease causing <i>Borrelia burgdorferi</i> that manifests arthritis and carditis and Apicomplexan protozoan, <i>Babesia microti</i> (<i>Bm</i>) that causes significant parasitemia associated with erythrocytopenia and haemoglobinuria. <i>B. burgdorferi</i> lacks typical TLR4 ligand lipopolysaccharides (LPS) and <i>Bm</i> TLR ligand(s) remain unknown. Only <i>Borrelia</i> lipoproteins that signal through TLR2 are established as PAMPs of these pathogens for TLR2/TLR4. Infection of C3H mice with each pathogen individually resulted in increase in the percentage of splenic B, T and FcR+ cells while their co-infection significantly diminished levels of these cells and caused increased <i>B. burgdorferi</i> burden in the specific organs. The most pronounced inflammatory arthritis was observed in co-infected C3H/HeJ mice. Parasitemia levels and kinetics of resolution of <i>Bm</i> in both mice strains were not significantly different. Transfected HEK293 cells showed pronounced signalling by <i>B. burgdorferi</i> through TLR2 and to some extent by TLR4 while <i>Bm</i> and infected erythrocytes did not show any response confirming our results in mice.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 9","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13350","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38941793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}