Infection and Immunity最新文献

{"title":"Do white-footed mice, the main reservoir of the Lyme disease pathogen in the United States, clinically respond to the borrelial tenancy?","authors":"Artem S Rogovskyy, Vasilis C Pliasas, Ryan Buhrer, Keith Lewy, Dominique J Wiener, Yoonsung Jung, Jonathan Bova, Yuliya Rogovska, Sun J Kim, Eunhye Grace Jeon","doi":"10.1128/iai.00382-24","DOIUrl":"https://doi.org/10.1128/iai.00382-24","url":null,"abstract":"<p><p>As white-footed mice, <i>Peromyscus leucopus</i>, are considered the primary animal reservoir of <i>Borreliella burgdorferi sensu stricto</i> (<i>Bb</i>), the main agent of Lyme disease (LD) in the United States, these animals represent the most relevant model to study borrelial spirochetes in the context of their natural life cycle. Previous studies have consistently demonstrated that although white-footed mice respond immunologically to the invasion of the Lyme pathogen, <i>P. leucopus</i> adults do not develop a clinically detectable disease. This tolerance, which is common for mammalian reservoirs of different pathogens, contrasts with detrimental anti-borrelial responses of C3H mice, a widely used animal model of LD, which always result in a clinical manifestation (e.g., arthritis). The current investigation is a follow-up of our recent study that already showed a relative quiescence of the spleen transcriptome for <i>Bb</i>-infected white-footed mice compared to the infected C3H mice. In an effort to identify the mechanism behind this tolerance, in this study, we have evaluated an extensive list of hematological and biochemical parameters measured in white-footed mice after their 70-day-long borrelial infection. Despite missing reference intervals for <i>Peromyscus</i> mice, our sex- and age-matched uninfected controls allowed us to assess the blood and serum parameters. In addition, for our assessment, we also utilized behavioral, immunological, and histological analyses. Collectively, by using the metrics reported herein, the present results have demonstrated clinical unresponsiveness of <i>P. leucopus</i> mice to the borrelial infection, presenting no restriction to a long-term host-pathogen co-existence.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0038224"},"PeriodicalIF":2.9,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619583","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 human gut microbiome in health and disease: time for a new chapter?","authors":"Jee-Yon Lee, Derek J Bays, Hannah P Savage, Andreas J Bäumler","doi":"10.1128/iai.00302-24","DOIUrl":"10.1128/iai.00302-24","url":null,"abstract":"<p><p>The gut microbiome, composed of the colonic microbiota and their host environment, is important for many aspects of human health. A gut microbiome imbalance (gut dysbiosis) is associated with major causes of human morbidity and mortality. Despite the central part our gut microbiome plays in health and disease, mechanisms that maintain homeostasis and properties that demarcate dysbiosis remain largely undefined. Here we discuss that sorting taxa into meaningful ecological units reveals that the availability of respiratory electron acceptors, such as oxygen, in the host environment has a dominant influence on gut microbiome health. During homeostasis, host functions that limit the diffusion of oxygen into the colonic lumen shelter a microbial community dominated by primary fermenters from atmospheric oxygen. In turn, primary fermenters break down unabsorbed nutrients into fermentation products that support host nutrition. This symbiotic relationship is disrupted when host functions that limit the luminal availability of host-derived electron acceptors become weakened. The resulting changes in the host environment drive alterations in the microbiota composition, which feature an elevated abundance of facultatively anaerobic microbes. Thus, the part of the gut microbiome that becomes imbalanced during dysbiosis is the host environment, whereas changes in the microbiota composition are secondary to this underlying cause. This shift in our understanding of dysbiosis provides a novel starting point for therapeutic strategies to restore microbiome health. Such strategies can either target the microbes through metabolism-based editing or strengthen the host functions that control their environment.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0030224"},"PeriodicalIF":2.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11556149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345961","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":"Molecular mechanisms of <i>Coxiella burnetii</i> formalin-fixed cellular vaccine reactogenicity.","authors":"A P Fratzke, J A Szule, S M Butler, E J van Schaik, J E Samuel","doi":"10.1128/iai.00335-24","DOIUrl":"10.1128/iai.00335-24","url":null,"abstract":"<p><p>Local and systemic reactogenic responses to Q-VAX have prevented licensing of this vaccine outside of Australia. These reactogenic responses occur in previously sensitized individuals and have not been well defined at the cellular level, in part because many studies have been done in guinea pigs that have limited molecular tools. We previously characterized a mouse model of reactogenicity where local reaction sites showed an influx of CD8+ and IFNγ-expressing IL17a+ CD4+ T cells consistent with a Th1 delayed-type hypersensitivity. In this study, we determined, using depletion and adoptive transfer experiments, that both anti-<i>Coxiella</i> antibodies and CD4+ T cells were essential for localized reactions at the site of vaccination. Furthermore, IFNγ depletion showed significant histological changes at the local reaction sites demonstrating the essential nature of this cytokine to reactogenicity. In addition to the cells and cytokines required for this response, we determined that whole cell vaccine (WCV) material remained at the site of vaccination for at least 26 weeks post-injection. Transmission electron microscopy (TEM) of these sites demonstrated intact rod-shaped bacteria at 2 weeks post-injection and partially degraded bacteria within macrophages at 26 weeks post-injection. Finally, because small cell variants (SCVs) are an environmentally stable form, we determined that local reactions were more severe when the WCV material was prepared with higher levels of SCVs compared to typical WCV or with higher levels of large cell variant (LCV). These studies support the hypothesis that antigen persistence at the site of injection contributes to this reactogenicity and that anti-<i>Coxiella</i> antibodies, CD4+ T cells, and IFNγ each contribute to this process.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0033524"},"PeriodicalIF":2.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11556133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361365","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":"Unveiling the impact of <i>Leptospira</i> TolC efflux protein on host tissue adherence, complement evasion, and diagnostic potential.","authors":"Saswat Hota, Manish Kumar","doi":"10.1128/iai.00419-24","DOIUrl":"10.1128/iai.00419-24","url":null,"abstract":"<p><p>The TolC family protein of <i>Leptospira</i> is a type I outer membrane efflux protein. Phylogenetic analysis revealed significant sequence conservation among pathogenic <i>Leptospira</i> species (83%-98% identity) compared with intermediate and saprophytic species. Structural modeling indicated a composition of six β-strands and 10 α-helices arranged in two repeats, resembling bacterial outer membrane efflux proteins. Recombinant TolC (rTolC), expressed in a heterologous host and purified via Ni-NTA chromatography, maintained its secondary structural integrity, as verified by circular dichroism spectroscopy. Polyclonal antibodies against rTolC detected native TolC expression in pathogenic <i>Leptospira</i> but not in nonpathogenic ones. Immunoassays and detergent fractionation assays indicated surface localization of TolC. The rTolC's recognition by sera from leptospirosis-infected hosts across species suggests its utility as a diagnostic marker. Notably, rTolC demonstrated binding affinity for various extracellular matrix components, including collagen and chondroitin sulfate A, as well as plasma proteins such as factor H, C3b, and plasminogen, indicating potential roles in tissue adhesion and immune evasion. Functional assays demonstrated that rTolC-bound FH retained cofactor activity for C3b cleavage, highlighting TolC's role in complement regulation. The rTolC protein inhibited both the alternative and the classical pathway-mediated membrane attack complex (MAC) deposition <i>in vitro</i>. Blocking surface-expressed TolC on leptospires using specific antibodies reduced FH acquisition by <i>Leptospira</i> and increased MAC deposition on the spirochete. These findings indicate that TolC contributes to leptospiral virulence by promoting host tissue colonization and evading the immune response, presenting it as a potential target for diagnostic and therapeutic strategies.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0041924"},"PeriodicalIF":2.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11556070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400164","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":"A single immunization of <i>Borreliella burgdorferi</i>-infected mice with Vanguard crLyme elicits robust antibody responses to diverse strains and variants of outer surface protein C.","authors":"Gavin Z Chambers, Kathryn M F Chambers, Richard T Marconi","doi":"10.1128/iai.00396-24","DOIUrl":"10.1128/iai.00396-24","url":null,"abstract":"<p><p>Lyme disease, caused by <i>Borreliella burgdorferi</i> and related species<i>,</i> is a growing health threat to companion animals across North America and Europe. Vaccination is an important preventive tool used widely in dogs living in, or near, endemic regions. In this report, we assessed anti-outer surface protein (Osp) A and anti-OspC antibody responses in <i>B. burgdorferi</i>-infected and -naïve mice (C3H/HeN) after immunization with a murine-optimized single dose of the Lyme disease subunit vaccine, Vanguard crLyme. crLyme is comprised of OspA and an OspC chimeritope-based immunogen designated as CH14. Mice that were infected and immunized developed higher levels of anti-OspC antibodies (Abs) than those infected only or that received one vaccine dose. The anti-OspC Abs that developed in the infected/immunized mice bound to all OspC variants tested (<i>n</i> = 22), whereas OspC Abs in serum from infected mice bound predominantly to the OspC variant (type A) produced by the infecting <i>B. burgdorferi</i> strain. Consistent with the absence of OspA expression in infected mammals, none of the infected mice developed Abs to OspA and did not develop anti-OspA Abs after single dose immunization. Lastly, serum from infected/immunized mice displayed significantly higher and broader killing activity than serum from non-immunized infected mice. The results of this study demonstrate that a single vaccination of actively infected mice results in strong anti-OspC Ab responses. This study contributes to our understanding of Ab responses to vaccination in actively infected mammals.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0039624"},"PeriodicalIF":2.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11556006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464292","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":"An anti-Shiga toxin VHH nanobody multimer protects mice against fatal toxicosis when administered intramuscularly as repRNA.","authors":"Sally R Robinson, Denise Ann Dayao, Jhon A Medina, Cara J Martone, Anne K Yauch, Troy Hinkley, Jesse H Erasmus, Charles B Shoemaker, Saul Tzipori","doi":"10.1128/iai.00239-24","DOIUrl":"10.1128/iai.00239-24","url":null,"abstract":"<p><p>Hemolytic uremic syndrome (HUS) is a systemic sequelae from gastrointestinal infection with Shiga toxin (Stx) producing <i>Escherichia coli</i> (STEC) that can result in acute kidney injury, lasting renal disease, and death. Despite a window for intervention between hemorrhagic diarrhea and onset of HUS, no specific therapies exist to prevent or treat HUS following STEC infection. Furthermore, there is no way to predict which patients with STEC will develop HUS or any rapid way to determine which Stx variant is present. To address this, we have broadened the therpay to neutralize additional toxin variants. It contains a multimer of nanobodies derived from camelid heavy chain antibody fragments (VHHs). An improved <u>V</u>HH-based <u>n</u>eutralizing <u>a</u>gent (VNA2) is delivered intramuscularly as RNA combined with LION nanoparticles rather than mRNA, that replicates on administration (repRNA), resulting in a rapidly circulating VNA that can bind systemic toxin. The RNA/VNA2-Stx administered intramuscularly prevents toxicity and death in a mouse model of acute Stx toxicity.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0023924"},"PeriodicalIF":2.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11556087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400163","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":"<i>Toxoplasma gondii</i> infection induces the expression of the chemokine CXCL16 in macrophages to promote chemoattraction of CXCR6⁺ cells.","authors":"Louis-Philippe Leroux, Visnu Chaparro, Alexandra Plouffe, Brent Johnston, Maritza Jaramillo","doi":"10.1128/iai.00309-24","DOIUrl":"10.1128/iai.00309-24","url":null,"abstract":"<p><p>CXCL16 is a multifaceted chemokine expressed by macrophages and other immune cells in response to viral and bacterial pathogens. However, few studies have investigated its role in parasitic infections. The obligate intracellular parasite <i>Toxoplasma gondii</i> (<i>T. gondii</i>) is the causative agent of toxoplasmosis, an infection with potentially deleterious consequences in immunocompromised individuals and the developing fetus of acutely infected pregnant women. Chemokines are critical mediators of host defense and, as such, dysregulation of their expression is a subversion strategy often employed by the parasite to ensure its survival. Herein, we report that types I and II <i>T. gondii</i> strains upregulated the expression of both transmembrane and soluble forms of CXCL16 in infected bone marrow-derived macrophages (BMDM). Exposure to soluble <i>T. gondii</i> antigens (STAg) and to excreted-secreted proteins (TgESP) led to the induction of CXCL16. <i>Cxcl16</i> mRNA abundance and CXCL16 protein levels increased in a time-dependent manner upon <i>T. gondii</i> infection. Importantly, conditioned medium (CM) collected from <i>T. gondii</i>-infected wild-type (WT) macrophage cultures promoted the migration of RAW264.7 cells expressing CXCR6, the cognate receptor of CXCL16, an effect that was significantly reduced by a neutralizing anti-CXCL16 antibody or use of CM from CXCL16 knockout (KO) macrophages. Lastly, <i>T. gondii</i>-driven CXCL16 expression appeared to modulate cytokine-induced (IL-4 + IL-13) alternative macrophage activation and M2 phenotypic marker expression. Further investigation is required to determine whether this chemokine contributes to the pathogenesis of toxoplasmosis and to elucidate the underlying molecular mechanisms.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0030924"},"PeriodicalIF":2.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11556035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464291","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":"Synergistic blockade of TIGIT and PD-L1 increases type-1 inflammation and improves parasite control during murine blood-stage <i>Plasmodium yoelii</i> non-lethal infection.","authors":"Rebecca S Dookie, Ana Villegas-Mendez, Antonn Cheeseman, Adam P Jones, Ruben Barroso, Jordan R Barrett, Simon J Draper, Chris J Janse, Jane L Grogan, Andrew S MacDonald, Kevin N Couper","doi":"10.1128/iai.00345-24","DOIUrl":"10.1128/iai.00345-24","url":null,"abstract":"<p><p>Pro-inflammatory immune responses are rapidly suppressed during blood-stage malaria but the molecular mechanisms driving this regulation are still incompletely understood. In this study, we show that the co-inhibitory receptors TIGIT and PD-1 are upregulated and co-expressed by antigen-specific CD4⁺ T cells (ovalbumin-specific OT-II cells) during non-lethal <i>Plasmodium yoelii</i> expressing ovalbumin (<i>Py</i>NL<i>-OVA</i>) blood-stage infection. Synergistic blockade of TIGIT and PD-L1, but not individual blockade of each receptor, during the early stages of infection significantly improved parasite control during the peak stages (days 10-15) of infection. Mechanistically, this protection was correlated with significantly increased plasma levels of IFN-γ, TNF, and IL-2, and an increase in the frequencies of IFN-γ-producing antigen-specific T-bet⁺ CD4⁺ T cells (OT-II cells), but not antigen-specific CD8⁺ T cells (OT-I cells), along with expansion of the splenic red pulp and monocyte-derived macrophage populations. Collectively, our study identifies a novel role for TIGIT in combination with the PD1-PD-L1 axis in regulating specific components of the pro-inflammatory immune response and restricting parasite control during the acute stages of blood-stage <i>Py</i>NL infection.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0034524"},"PeriodicalIF":2.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11556036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345960","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":"<i>Orientia tsutsugamushi</i> infection reduces host gluconeogenic but not glycolytic substrates.","authors":"Savannah E Sanchez, Travis J Chiarelli, Margaret A Park, Jason A Carlyon","doi":"10.1128/iai.00284-24","DOIUrl":"10.1128/iai.00284-24","url":null,"abstract":"<p><p><i>Orientia tsutsugamushi</i> a causal agent of scrub typhus, is an obligate intracellular bacterium that, akin to other rickettsiae, is dependent on host cell-derived nutrients for survival and thus pathogenesis. Based on limited experimental evidence and genome-based <i>in silico</i> predictions, <i>O. tsutsugamushi</i> is hypothesized to parasitize host central carbon metabolism (CCM). Here, we (re-)evaluated <i>O. tsutsugamushi</i> dependency on host cell CCM as initiated by glucose and glutamine. <i>Orientia</i> infection had no effect on host glucose and glutamine consumption or lactate accumulation, indicating no change in overall flux through CCM. However, host cell mitochondrial activity and ATP levels were reduced during infection and correspond with lower intracellular glutamine and glutamate pools. To further probe the essentiality of host CCM in <i>O. tsutsugamushi</i> proliferation, we developed a minimal medium for host cell cultivation and paired it with chemical inhibitors to restrict the intermediates and processes related to glucose and glutamine metabolism. These conditions failed to negatively impact <i>O. tsutsugamushi</i> intracellular growth, suggesting the bacterium is adept at scavenging from host CCM. Accordingly, untargeted metabolomics was utilized to evaluate minor changes in host CCM metabolic intermediates across <i>O. tsutsugamushi</i> infection and revealed that pathogen proliferation corresponds with reductions in critical CCM building blocks, including amino acids and TCA cycle intermediates, as well as increases in lipid catabolism. This study directly correlates <i>O. tsutsugamushi</i> proliferation to alterations in host CCM and identifies metabolic intermediates that are likely critical for pathogen fitness.IMPORTANCEObligate intracellular bacterial pathogens have evolved strategies to reside and proliferate within the eukaryotic intracellular environment. At the crux of this parasitism is the balance between host and pathogen metabolic requirements. The physiological basis driving <i>O. tsutsugamushi</i> dependency on its mammalian host remains undefined. By evaluating alterations in host metabolism during <i>O. tsutsugamushi</i> proliferation, we discovered that bacterial growth is independent of the host's nutritional environment but appears dependent on host gluconeogenic substrates, including amino acids. Given that <i>O. tsutsugamushi</i> replication is essential for its virulence, this study provides experimental evidence for the first time in the post-genomic era of metabolic intermediates potentially parasitized by a scrub typhus agent.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0028424"},"PeriodicalIF":2.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11556148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345959","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":"Establishment of CD1b-restricted immunity to lipid antigens in the pulmonary response to <i>Mycobacterium tuberculosis</i> infection.","authors":"Macallister C Harris, Hadley E Gary, Sarah K Cooper, David F Ackart, James E DiLisio, Randall J Basaraba, Tan-Yun Cheng, Ildiko van Rhijn, D Branch Moody, Brendan K Podell","doi":"10.1128/iai.00380-24","DOIUrl":"10.1128/iai.00380-24","url":null,"abstract":"<p><p>CD1 is an antigen-presenting glycoprotein homologous to MHC I; however, CD1 proteins present lipid rather than peptide antigens. CD1 proteins are well established to present lipid antigens of <i>Mycobacterium tuberculosis</i> (Mtb) to T cells, but understanding the role of CD1-restricted immunity <i>in vivo</i> in response to Mtb infection has been limited by the availability of animal models naturally expressing the CD1 proteins implicated in human response: CD1a, CD1b, and CD1c. Guinea pigs, in contrast to other rodent models, express four CD1b orthologs, and here we utilize the guinea pig to establish the kinetics of gene and protein expression of CD1b orthologs, as well as the Mtb lipid-antigen and CD1b-restricted immune response at the tissue level over the course of Mtb infection. Our results indicate transient upregulation of CD1b expression during the effector phase of adaptive immunity that wanes with disease chronicity. Gene expression indicates that the upregulation of CD1b is the result of transcriptional induction across all CD1b orthologs. We show high CD1b3 expression on B cells, and identify CD1b3 as the predominant CD1b ortholog in pulmonary granuloma lesions. We identify <i>ex vivo</i> cytotoxic activity directed against CD1b that parallels the kinetic changes in CD1b expression in Mtb-infected lungs and spleen. This study confirms that CD1b expression is modulated by Mtb infection in lung and spleen, leading to pulmonary and extrapulmonary CD1b-restricted immunity as a component of the antigen-specific response to Mtb infection.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0038024"},"PeriodicalIF":2.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568336","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}