Infection and Immunity最新文献

{"title":"IL-22-dependent responses and their role during <i>Citrobacter rodentium</i> infection.","authors":"Karine Melchior, Romana R Gerner, Suzana Hossain, Sean-Paul Nuccio, Cristiano Gallina Moreira, Manuela Raffatellu","doi":"10.1128/iai.00099-24","DOIUrl":"10.1128/iai.00099-24","url":null,"abstract":"<p><p>The mouse pathogen <i>Citrobacter rodentium</i> is utilized as a model organism for studying infections caused by the human pathogens enteropathogenic <i>Escherichia coli</i> (EPEC) and enterohemorrhagic <i>E. coli</i> (EHEC) and to elucidate mechanisms of mucosal immunity. In response to <i>C. rodentium</i> infection, innate lymphoid cells and T cells secrete interleukin (IL)-22, a cytokine that promotes mucosal barrier function. IL-22 plays a pivotal role in enabling mice to survive and recover from <i>C. rodentium</i> infection, although the exact mechanisms involved remain incompletely understood. Here, we investigated whether particular components of the host response downstream of IL-22 contribute to the cytokine's protective effects during <i>C. rodentium</i> infection. In line with previous research, mice lacking the IL-22 gene (<i>Il22</i>^-/- mice) were highly susceptible to <i>C. rodentium</i> infection. To elucidate the role of specific antimicrobial proteins modulated by IL-22, we infected the following knockout mice: <i>S100A9</i>^-/- (calprotectin), <i>Lcn2</i>^-/- (lipocalin-2), <i>Reg3b</i>^-/- (Reg3β), <i>Reg3g</i>^-/- (Reg3γ), and <i>C3</i>^-/- (C3). All knockout mice tested displayed a considerable level of resistance to <i>C. rodentium</i> infection, and none phenocopied the lethality observed in <i>Il22</i>^-/- mice. By investigating another arm of the IL-22 response, we observed that <i>C. rodentium</i>-infected <i>Il22^-/</i>^- mice exhibited an overall decrease in gene expression related to intestinal barrier integrity as well as significantly elevated colonic inflammation, gut permeability, and pathogen levels in the spleen. Taken together, these results indicate that host resistance to lethal <i>C. rodentium</i> infection may depend on multiple antimicrobial responses acting in concert, or that other IL-22-regulated processes, such as tissue repair and maintenance of epithelial integrity, play crucial roles in host defense to attaching and effacing pathogens.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11075456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plant phenolics inhibit focal adhesion kinase and suppress host cell invasion by uropathogenic <i>Escherichia coli</i>.","authors":"Adam J Lewis, Amanda C Richards, Alejandra A Mendez, Bijaya K Dhakal, Tiffani A Jones, Jamie L Sundsbak, Danelle S Eto, Alexis A Rousek, Matthew A Mulvey","doi":"10.1128/iai.00080-24","DOIUrl":"10.1128/iai.00080-24","url":null,"abstract":"<p><p>Traditional folk treatments for the prevention and management of urinary tract infections (UTIs) and other infectious diseases often include plants and plant extracts that are rich in phenolic compounds. These have been ascribed a variety of activities, including inhibition of bacterial interactions with host cells. Here, we tested a panel of four well-studied phenolic compounds-caffeic acid phenethyl ester (CAPE), resveratrol, catechin, and epigallocatechin gallate-for the effects on host cell adherence and invasion by uropathogenic <i>Escherichia coli</i> (UPEC). These bacteria, which are the leading cause of UTIs, can bind and subsequently invade bladder epithelial cells via an actin-dependent process. Intracellular UPEC reservoirs within the bladder are often protected from antibiotics and host defenses and likely contribute to the development of chronic and recurrent infections. In cell culture-based assays, only resveratrol had a notable negative effect on UPEC adherence to bladder cells. However, both CAPE and resveratrol significantly inhibited UPEC entry into the host cells, coordinate with attenuated phosphorylation of the host actin regulator Focal Adhesion Kinase (FAK or PTK2) and marked increases in the numbers of focal adhesion structures. We further show that the intravesical delivery of resveratrol inhibits UPEC infiltration of the bladder mucosa in a murine UTI model and that resveratrol and CAPE can disrupt the ability of other invasive pathogens to enter host cells. Together, these results highlight the therapeutic potential of molecules like CAPE and resveratrol, which could be used to augment antibiotic treatments by restricting pathogen access to protective intracellular niches.IMPORTANCEUrinary tract infections (UTIs) are exceptionally common and increasingly difficult to treat due to the ongoing rise and spread of antibiotic-resistant pathogens. Furthermore, the primary cause of UTIs, uropathogenic <i>Escherichia coli</i> (UPEC), can avoid antibiotic exposure and many host defenses by invading the epithelial cells that line the bladder surface. Here, we identified two plant-derived phenolic compounds that disrupt activation of the host machinery needed for UPEC entry into bladder cells. One of these compounds, resveratrol, effectively inhibited UPEC invasion of the bladder mucosa in a mouse UTI model, and both phenolic compounds significantly reduced host cell entry by other invasive pathogens. These findings suggest that select phenolic compounds could be used to supplement existing antibacterial therapeutics by denying uropathogens shelter within host cells and tissues and help explain some of the benefits attributed to traditional plant-based medicines.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11075462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140293458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peptidoglycan fragment release and NOD activation by commensal <i>Neisseria</i> species from humans and other animals.","authors":"Tiffany N Harris-Jones, Jia Mun Chan, Kathleen T Hackett, Nathan J Weyand, Ryan E Schaub, Joseph P Dillard","doi":"10.1128/iai.00004-24","DOIUrl":"10.1128/iai.00004-24","url":null,"abstract":"<p><p><i>Neisseria gonorrhoeae</i>, a human restricted pathogen, releases inflammatory peptidoglycan (PG) fragments that contribute to the pathophysiology of pelvic inflammatory disease. The genus <i>Neisseria</i> is also home to multiple species of human- or animal-associated <i>Neisseria</i> that form part of the normal microbiota. Here we characterized PG release from the human-associated nonpathogenic species <i>Neisseria lactamica</i> and <i>Neisseria mucosa</i> and animal-associated <i>Neisseria</i> from macaques and wild mice. An <i>N. mucosa</i> strain and an <i>N. lactamica</i> strain were found to release limited amounts of the proinflammatory monomeric PG fragments. However, a single amino acid difference in the PG fragment permease AmpG resulted in increased PG fragment release in a second <i>N. lactamica</i> strain examined. <i>Neisseria</i> isolated from macaques also showed substantial release of PG monomers. The mouse colonizer <i>Neisseria musculi</i> exhibited PG fragment release similar to that seen in <i>N. gonorrhoeae</i> with PG monomers being the predominant fragments released. All the human-associated species were able to stimulate NOD1 and NOD2 responses. <i>N. musculi</i> was a poor inducer of mouse NOD1, but <i>ldcA</i> mutation increased this response. The ability to genetically manipulate <i>N. musculi</i> and examine effects of different PG fragments or differing amounts of PG fragments during mouse colonization will lead to a better understanding of the roles of PG in <i>Neisseria</i> infections. Overall, we found that only some nonpathogenic <i>Neisseria</i> have diminished release of proinflammatory PG fragments, and there are differences even within a species as to types and amounts of PG fragments released.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11075463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of the hypothetical protein BB0616 in the murine infection of Borrelia burgdorferi","authors":"Christina Thompson, Connor Waldron, Sierra George, Zhiming Ouyang","doi":"10.1128/iai.00090-24","DOIUrl":"https://doi.org/10.1128/iai.00090-24","url":null,"abstract":"Lyme disease is the most common vector-borne infection, with an estimated 476,000\u0000new cases annually in the United States (1, 2). Clinical manifestations range from characteristic skin lesions called “erythema\u0000migrans” to carditis, arthritis, and neuroborreliosis. This disease is caused by the\u0000spirochetal pathogen Borrelia burgdorferi (also known as Borreliella burgdorferi), which is transmitted to humans through hematophagous bites of an arthropod tick\u0000vector (usually Ixodes ticks) (3–5). B. burgdorferi is maintained in nature through an infectious cycle involving ticks and mammalian\u0000hosts. The acquisition of B. burgdorferi occurs when newly hatched larvae feed on infected reservoir hosts, e.g., small rodents,\u0000during which B. burgdorferi enters the ticks together with the bloodmeal and then colonizes the tick midgut.\u0000Following colonization, spirochetes reside in this nutritionally limited environment\u0000through the molt into the nymphal stage. When nymphs attach to and take a bloodmeal\u0000on the subsequent hosts, spirochetes traverse the tick midgut peritrophic membrane,\u0000migrate through the hemocoel to the salivary gland, and then are deposited into the\u0000host skin to initiate infection. Once in the host, B. burgdorferi disseminates hematogenously into distant organs and causes tissue damage.","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140827642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innate phase production of IFN-γ by memory and effector T cells expressing early activation marker CD69 during infection with Cryptococcus deneoformans in the lungs","authors":"Anna Miyahara, Aya Umeki, Ko Sato, Toshiki Nomura, Hideki Yamamoto, Tomomitsu Miyasaka, Daiki Tanno, Ikumi Matsumoto, Tong Zong, Takafumi Kagesawa, Akiho Oniyama, Kotone Kawamura, Xiaoliang Yuan, Rin Yokoyama, Yuki Kitai, Emi Kanno, Hiromasa Tanno, Hiromitsu Hara, Sho Yamasaki, Shinobu Saijo, Yoichiro Iwakura, Keiko Ishii, Kazuyoshi Kawakami","doi":"10.1128/iai.00024-24","DOIUrl":"https://doi.org/10.1128/iai.00024-24","url":null,"abstract":"The two sister species, Cryptococcus neoformans (formerly C. neoformans var. grubii, serotype A) and C. deneoformans (formerly C. neoformans var. neoformans, serotype D), are yeast-type fungal pathogens characterized by thick capsules composed\u0000of polysaccharides such as glucuronoxylomannan and galactoxylomannan (1). These fungi grow in pigeon droppings and enter the lungs via an airborne route.\u0000While most healthy individuals experience asymptomatic infection, marked by granulomatous\u0000lesions in the lungs caused by these fungi, immunocompromised hosts with severely\u0000impaired cellular immunity, such as those with AIDS, frequently suffer from severe\u0000lung lesions and disseminated infections that extend to the central nervous system\u0000(2).","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140827899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The CpxRA two-component system of adherent and invasive Escherichia coli contributes to epithelial cell invasion and early-stage intestinal fitness in a dysbiotic mouse model mediated by type 1 fimbriae expression","authors":"Tsuyoshi Miki, Masahiro Ito, Nobuhiko Okada, Takeshi Haneda","doi":"10.1128/iai.00132-24","DOIUrl":"https://doi.org/10.1128/iai.00132-24","url":null,"abstract":"Crohn’s disease (CD) is an inflammatory bowel disease that is represented as a chronic\u0000inflammatory disorder of the gastrointestinal tract (1, 2). Although the detailed etiology of CD is still unclear, several factors appear to\u0000be involved in the onset and progression of CD, including genetic, immunological,\u0000and infectious factors (3–5). Notably, gut dysbiosis accompanied by gastrointestinal inflammation is the most\u0000common manifestation (6, 7). Given that gut dysbiosis is defined by decreased bacterial diversity and an imbalanced\u0000microbiota composition, it is speculated that certain bacteria, known as pathobionts,\u0000typically existing in symbiosis but capable of triggering disease under specific conditions,\u0000are involved in CD. To date, some bacterial species have been identified as suspicious\u0000(6–14). Among such bacteria, a pathobiont, adherent and invasive Escherichia coli (AIEC), is significantly prevalent in CD patients and has been widely accepted to\u0000be linked to CD (12, 15–18). AIEC strongly adheres to and invades intestinal epithelial cells, penetrates the\u0000epithelial barrier, survives within macrophages, moves to deep tissues, and induces\u0000inflammatory responses, along with secreting proinflammatory cytokines (19).","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140827483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pushing boundaries: mechanisms enabling bacterial pathogens to spread between cells.","authors":"Julie E. Raab, Desmond J Hamilton, Tucker B. Harju, T. N. Huynh, Brian C. Russo","doi":"10.1128/iai.00524-23","DOIUrl":"https://doi.org/10.1128/iai.00524-23","url":null,"abstract":"For multiple intracellular bacterial pathogens, the ability to spread directly into adjacent epithelial cells is an essential step for disease in humans. For pathogens such as Shigella, Listeria, Rickettsia, and Burkholderia, this intercellular movement frequently requires the pathogens to manipulate the host actin cytoskeleton and deform the plasma membrane into structures known as protrusions, which extend into neighboring cells. The protrusion is then typically resolved into a double-membrane vacuole (DMV) from which the pathogen quickly escapes into the cytosol, where additional rounds of intercellular spread occur. Significant progress over the last few years has begun to define the mechanisms by which intracellular bacterial pathogens spread. This review highlights the interactions of bacterial and host factors that drive mechanisms required for intercellular spread with a focus on how protrusion structures form and resolve.","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140658081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Controlling Candida: immune regulation of commensal fungi in the gut.","authors":"Owen Jensen, Emma Trujillo, Luke Hanson, Kyla S. Ost","doi":"10.1128/iai.00516-23","DOIUrl":"https://doi.org/10.1128/iai.00516-23","url":null,"abstract":"The intestinal microbiome harbors fungi that pose a significant risk to human health as opportunistic pathogens and drivers of inflammation. Inflammatory and autoimmune diseases are associated with dysbiotic fungal communities and the expansion of potentially pathogenic fungi. The gut is also the main reservoir for disseminated fungal infections. Immune interactions are critical for preventing commensal fungi from becoming pathogenic. Significant strides have been made in defining innate and adaptive immune pathways that regulate intestinal fungi, and these discoveries have coincided with advancements in our understanding of the fungal molecular pathways and effectors involved in both commensal colonization and pathogenesis within the gut. In this review, we will discuss immune interactions important for regulating commensal fungi, with a focus on how specific cell types and effectors interact with fungi to limit their colonization or pathogenic potential. This will include how innate and adaptive immune pathways target fungi and orchestrate antifungal immune responses, in addition to how secreted immune effectors, such as mucus and antimicrobial peptides, regulate fungal colonization and inhibit pathogenic potential. These immune interactions will be framed around our current understanding of the fungal effectors and pathways regulating colonization and pathogenesis within this niche. Finally, we highlight important unexplored mechanisms by which the immune system regulates commensal fungi in the gut.","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140673618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The prostaglandin D2 antagonist asapiprant ameliorates clinical severity in young hosts infected with invasive Streptococcus pneumoniae","authors":"Manmeet BhallaSydney HerringAlexsandra LenhardJoshua R. WheelerFred AswadKlaus KlumppJustin ReboYan WangKevin WilhelmsenKristen FortneyElsa N. Bou Ghanem1Department of Microbiology and Immunology, School of Medicine, University at Buffalo, Buffalo, New York, USA2Department of Pathology, Stanford University, Stanford, California, USA3BIOAGE Labs Inc., Richmond, California, USA, Nancy E. Freitag","doi":"10.1128/iai.00522-23","DOIUrl":"https://doi.org/10.1128/iai.00522-23","url":null,"abstract":"Infection and Immunity, Ahead of Print. <br/>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140616847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CCR2-dependent CX3CR1+ colonic macrophages promote Enterococcus faecalis dissemination","authors":"Kevin C. Jennings, Kaitlin E. Johnson, Michael A. Hayward, Christopher J. Kristich, Nita H. Salzman","doi":"10.1128/iai.00006-24","DOIUrl":"https://doi.org/10.1128/iai.00006-24","url":null,"abstract":"Enterococci are Gram-positive commensal bacteria found in the gastrointestinal tract\u0000of most mammals. Although enterococci are typically non-pathogenic, they are intrinsically\u0000resistant to cephalosporin antibiotics, and treatment with cephalosporins can lead\u0000to opportunistic infections in humans and mice (1, 2). Currently, enterococci are the third leading cause of infectious endocarditis,\u0000with Enterococcus faecalis contributing to &gt;90% of reported enterococcus-related cases (3, 4). Furthermore, the rising prevalence of vancomycin-resistant enterococci, predominantly\u0000Enterococcus faecium, has made enterococci a leading cause of hospital-acquired infections in the United\u0000States (5). Nevertheless, most individuals colonized with enterococci, including E. faecalis or E. faecium, do not succumb to infections (6, 7). This highlights the generally commensal nature of enterococci but suggests a gap\u0000in our understanding of the preconditions for opportunistic infections by these pathobionts.\u0000To date, the mechanisms by which commensal enterococci subvert host immunity to become\u0000pathogenic remain poorly understood.","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140616844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}