Jonathan I. Silverberg, Tamar A. Smith-Norowitz, Stephan Kohlhoff, Rauno Joks
{"title":"Phosphorylated p38 MAP kinase expression by leucocytes is increased in allergic humans and associated with IgE responses","authors":"Jonathan I. Silverberg, Tamar A. Smith-Norowitz, Stephan Kohlhoff, Rauno Joks","doi":"10.1111/sji.13343","DOIUrl":"https://doi.org/10.1111/sji.13343","url":null,"abstract":"Mitogen-activated protein kinases (MAPK) activate cascades that regulate cell proliferation, differentiation and death. Phosphorylated (phos-)p38 MAPK is a cell-signalling pathway associated with Th2 cytokine responses, which is required for immunoglobulin (Ig)E production. It is unknown whether MAPK are associated with IgE production. We examine the evidence linking p38 MAPK to inflammatory responses. Phos-p38, extracellular signal-related kinase (ERK) and c-JUN-n terminal (JNK) MAPK expression by blood leucocyte subsets and levels of serum Igs were measured in blood from adults with asthma and/or rhinoconjunctivitis (<i>N</i> = 28) and non-asthma (<i>N</i> = 10) (flow cytometry, microfluorenzymeimmunoassay). Peripheral blood mononuclear cells (PBMC) from allergic subjects were cultured for 10 days ± anti-CD40/recombinant IL-4 ± inhibitor of phos-P38. Culture supernatants were assayed for IgE (ELISA). Phos-p38 MAPK expression by all leucocyte subsets of allergic subjects was associated with serum IgE levels (<i>p</i> ≤ 0.01), after adjusting for cell counts, age, sex, race and smoking status (<i>p</i> ≤ 0.04). Leucocyte expression of phos-ERK and JNK did not correlate with IgE <i>(p</i> = 0.09–0.99). Instead, phos-ERK expression was associated with serum IgG. When PBMC from atopic subjects were cultured for 10 days with anti-CD40/rhIL-4, IgE levels were 26.2 ± 18 ng/mL. Inclusion of SB202190 (5–20 μg/mL), a specific inhibitor of phos-p38 MAPK, in culture suppressed IgE production in dose-dependent manner, with peak suppression obtained with SB202190 at 20 μg/mL (82.1% ± 11.8) (<i>p</i> = 0.0001), with virtually no cytotoxicity (<5%). Different MAPK pathways may be associated with IgE (p38) and IgG (ERK) responses. Phos-p38 MAPK can be a potential anti-allergy drug target.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"44 5","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138509061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nathaniel Edward Bennett Saidu, Miriam Aarsund, Eva Sørensen, Maria Stensland, Tuula Anneli Nyman, Aina Ulvmoen, Yunjie Wu, Marit Inngjerdingen
{"title":"Identifying a core protein signature of small extracellular vesicles derived from B-cell precursor acute lymphoblastic leukaemia","authors":"Nathaniel Edward Bennett Saidu, Miriam Aarsund, Eva Sørensen, Maria Stensland, Tuula Anneli Nyman, Aina Ulvmoen, Yunjie Wu, Marit Inngjerdingen","doi":"10.1111/sji.13341","DOIUrl":"https://doi.org/10.1111/sji.13341","url":null,"abstract":"Acute paediatric leukaemia is diagnosed and monitored via bone marrow aspirate assessment of blasts as a measure of minimal residual disease. Liquid biopsies in the form of blood samples could greatly reduce the need for invasive bone marrow aspirations, but there are currently no blood markers that match the sensitivity of bone marrow diagnostics. Circulating extracellular vesicles (EVs) represent candidate biomarkers that may reflect the blast burden in bone marrow, and several studies have reported on the utility of EVs as biomarkers for adult haematological malignancies. Increased levels of EVs have been reported for several haematological malignancies, and we similarly report here elevated EV concentrations in plasma from paediatric BCP-ALL patients. Plasma EVs are very heterogeneous in terms of their cellular origin, thus identifying a cancer selective EV-marker is challenging. Here, we undertook a reductionistic approach to identify protein markers selectively associated to plasma EVs derived from BCP-ALL patients. The EV proteome of primary BCP-ALL cell-derived EVs were compared against EVs from healthy donor B cells and the BCP-ALL cell line REH, and further against EVs isolated from plasma of healthy paediatric donors and paediatric BCP-ALL patients. With this approach, we identified a signature of 6 proteins (CD317, CD38, IGF2BP1, PCNA, CSDE1, and GPR116) that were specifically identified in BCP-ALL derived EVs only and not in healthy control EVs, and that could be exploited as diagnostic biomarkers.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"43 12","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138509065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Veronika Krmeská, Lei Shen, Susanne Nylén, Pryscilla Fanini Wowk, Antonio Gigliotti Rothfuchs
{"title":"BCG infection dose guides dendritic cell migration and T cell priming in the draining lymph node","authors":"Veronika Krmeská, Lei Shen, Susanne Nylén, Pryscilla Fanini Wowk, Antonio Gigliotti Rothfuchs","doi":"10.1111/sji.13342","DOIUrl":"https://doi.org/10.1111/sji.13342","url":null,"abstract":"In contrast to delayed-type hypersensitivity (DTH) and other hallmark reactions of cell-mediated immunity that correlate with vaccine-mediated protection against <i>Mycobacterium tuberculosis</i>, the contribution of vaccine dose on responses that emerge early after infection in the skin with Bacille Calmette–Guérin (BCG) is not well understood. We used a mouse model of BCG skin infection to study the effect of BCG dose on the relocation of skin Dendritic cells (DCs) to draining lymph node (DLN). <i>Mycobacterium</i> antigen 85B-specific CD4<sup>+</sup> P25 T cell-receptor transgenic (P25 TCRTg) cells were used to probe priming to BCG in DLN. DC migration and T cell priming were studied across BCG inocula that varied up to 100-fold (10<sup>4</sup> to 10<sup>6</sup> Colony-forming units—CFUs). In line with earlier results in guinea pigs, DTH reaction in our model correlated with BCG dose. Importantly, priming of P25 TCRTg cells in DLN also escalated in a dose-dependent manner, peaking at day 6 after infection. Similar dose-escalation effects were seen for DC migration from infected skin and the accompanying transport of BCG to the DLN. BCG-triggered upregulation of co-stimulatory molecules on migratory DCs was restricted to the first 24 hour after infection and was independent of BCG dose over a 10-fold range (10<sup>5</sup> to 10<sup>6</sup> CFUs). The dose seemed to be a determinant of the number of total skin DCs that move to the DLN. In summary, our results support the use of higher BCG doses to detect robust DC migration and T cell priming.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"45 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138509060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dina Leth Møller, Søren Schwartz Sørensen, Michael Perch, Finn Gustafsson, Annemette Hald, Andreas Delhbæk Knudsen, Ranya Abdulovski, Nicoline Stender Arentoft, Jens Lundgren, Allan Rasmussen, Sisse Rye Ostrowski, Susanne Dam Nielsen
{"title":"<scp>Anti‐inflammatory</scp> and <scp>antioxidative</scp> actions of tacrolimus (<scp>FK506</scp>) on human microglial <scp>HMC3</scp> cell line","authors":"Fatma Gonca Kocanci, Azize Yasemin Goksu","doi":"10.1111/sji.13339","DOIUrl":"https://doi.org/10.1111/sji.13339","url":null,"abstract":"Abstract Microglial cells are indispensable for the normal development and functioning of neurons in the central nervous system, where they play a crucial role in maintaining brain homeostasis by surveilling the microenvironment for signs of injury or stress and responding accordingly. However, in neurodegenerative diseases, the density and phenotypes of microglial cells undergo changes, leading to chronic activation and inflammation. Shifting the focus from neurons to microglia in drug discovery for neurodegenerative diseases has become an important therapeutic target. This study was aimed to investigate the potential of Tacrolimus (FK506) an FDA‐approved calcineurin inhibitor, to modulate the pathology of neurodegenerative diseases through anti‐inflammatory and antioxidative effects on microglial activation. The human microglia clone 3 (HMC3) cells were exposed to 1 μg/mL LPS in the presence and absence of doses of FK506. Survival rates of cells were determined using the 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐Diphenyltetrazolium Bromide (MTT) method. Morphological evaluation of cells showed that FK506 restored the normal morphology of activated microglia. Furthermore, FK506 treatment increases the total antioxidant capacity and reduces the total oxidative capacity, indicating its potential antioxidant effects. Data from ELISA and RT‐PCR analyses showed that LPS abolished its promoting effects on the release of proinflammatory IL‐1β and IL‐6 cytokines in HMC3 cells, reflecting the anti‐inflammatory effect of FK506. These findings support the idea that FK506 could be a promising therapeutic agent for neurodegenerative diseases by modulating microglial activation and reducing inflammation and oxidative stress.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"126 49","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136352249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Transient hypogammaglobulinemia of infancy and unclassified syndromic immunodeficiencies are highly common in oesophageal atresia patients","authors":"Hilmican Ulman, Ayşe Aygün, Deniz Çağlar, Zafer Dökümcü, Ezgi Topyıldız, Ata Erdener, Güzide Aksu, Neslihan Edeer Karaca, Coşkun Özcan, Necil Kütükçüler","doi":"10.1111/sji.13338","DOIUrl":"https://doi.org/10.1111/sji.13338","url":null,"abstract":"Abstract Due to the high rate of post‐operative sepsis and other infectious complications, a routine immunological screening protocol has been initiated since 2015 in our paediatric surgery clinic for all patients admitted with oesophageal atresia (EA) and warrant a delayed definitive treatment. In our study, we aimed to evaluate the immunodeficiencies in EA patients, by comparing them to healthy age‐matched controls. As a prospective cohort study, EA patients admitted between 2015 and 2022, who had their definitive operation after the newborn period (>28 days of age) were included. On admission, serum concentrations of IgG, IgA, IgM, lymphocyte subset levels, C3 and C4 levels, specific IgG antibody responses against hepatitis B, hepatitis A, measles, varicella zoster were evaluated. The patients were age‐matched with healthy controls to compare the results and followed up until three years of age. If a humoral immunodeficiency was detected, intravenous immunoglobulin treatment was administered before major oesophageal surgery and during follow‐up. 31 EA patients (18 M/13F) with a mean age of 13.3 ± 9.0 months were compared with 40 age‐matched healthy controls. Mean serum IgG levels were found to be statistically lower than controls in all age groups ( P < .05). Transient hypogammaglobulinemia of infancy (THI) and unclassified syndromic immunodeficiencies (USI) were found to be strikingly high, accounting for 29.0% and 22.5%, respectively, adding up to 51.5% of EA patients. This is the first study evaluating immunodeficiencies in EA patients found in the reviewed literature. More than half of EA patients that required delayed surgery had humoral immunodeficiency, so preoperative screening and immunology referral may improve patient outcomes.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"9 11","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135038172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ke Chen, Xin Gu, Shufan Yang, Rui Tao, Menglei Fan, Wenyang Bao, Xiaoyun Wang
{"title":"Research progress on intestinal tissue‐resident memory T cells in inflammatory bowel disease","authors":"Ke Chen, Xin Gu, Shufan Yang, Rui Tao, Menglei Fan, Wenyang Bao, Xiaoyun Wang","doi":"10.1111/sji.13332","DOIUrl":"https://doi.org/10.1111/sji.13332","url":null,"abstract":"Abstract Tissue‐resident memory T (T RM ) cells are a recently discovered subpopulation of memory T cells that reside in non‐lymphoid tissues such as the intestine and skin and do not enter the bloodstream. The intestine encounters numerous pathogens daily. Intestinal mucosal immunity requires a balance between immune responses to pathogens and tolerance to food antigens and symbiotic microbiota. Therefore, intestinal T RM cells exhibit unique characteristics. In healthy intestines, T RM cells induce necessary inflammation to strengthen the intestinal barrier and inhibit bacterial translocation. During intestinal infections, T RM cells rapidly eliminate pathogens by proliferating, releasing cytokines, and recruiting other immune cells. Moreover, certain T RM cell subsets may have regulatory functions. The involvement of T RM cells in inflammatory bowel disease (IBD) is increasingly recognized as a critical factor. In IBD, the number of pro‐inflammatory T RM cells increases, whereas the number of regulatory subgroups decreases. Additionally, the classic markers, CD69 and CD103, are not ideal for intestinal T RM cells. Here, we review the phenotype, development, maintenance, and function of intestinal T RM cells, as well as the latest findings in the context of IBD. Further understanding of the function of intestinal T RM cells and distinguishing their subgroups is crucial for developing therapeutic strategies to target these cells.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"9 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135992739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tine Simensen Oldereid, Xiaojun Jiang, Kathrine Sivertsen Nordhus, Andrea Ponzetta, Jørgen Vildershøj Bjørnholt, Niklas K. Björkström, Espen Melum, Henrik Rasmussen
{"title":"Role of bacteria and microbial metabolites in immune modulation during early life","authors":"Tine Simensen Oldereid, Xiaojun Jiang, Kathrine Sivertsen Nordhus, Andrea Ponzetta, Jørgen Vildershøj Bjørnholt, Niklas K. Björkström, Espen Melum, Henrik Rasmussen","doi":"10.1111/sji.13336","DOIUrl":"https://doi.org/10.1111/sji.13336","url":null,"abstract":"Abstract Host–microbiome interplay from birth is essential for immune imprinting and tuning. Live gut microbes and microbial‐derived metabolites regulate the development and modulation of the immune system, but whether microbial metabolites solely are sufficient to induce immune maturation remains unclear. Sterile faecal filtrates (FFT) were generated from murine gut contents. Newborn germ‐free (GF) mice were treated twice daily with FFT (GF‐FFT) or saline (GF‐NaCl) from post‐natal day 5 until 4 weeks of age. A third group of GF neonates were conventionalized by the transfer of caecal microbiota with live gut microbes. Host immune compartments were comprehensively immunophenotyped and systemically analysed in all available immune‐related organs using flow cytometry. Oral FFT was associated with reduced survival among neonates (n = 7/19; 36.8% mortality), while saline treatment was well tolerated (n = 1/17, 5.9% mortality). Four‐week‐old FFT‐treated pups were comparable in body weight to GF‐NaCl, and the major B‐cell, conventional T‐cell and unconventional T‐cell subsets were unchanged from saline‐treated mice. Live bacteria administered during early life induced clear changes in proportions of B cells, T cells and T‐cell subsets in all mucosal tissues and secondary lymphoid organs compared to GF‐FFT, including restoration of intestinal natural killer T (NKT) cells with characteristics similar to conventional pups. Our findings show that oral administration of a FFT made of microbial metabolites, antigens and bacteriophages alone is insufficient to induce normal immune development elicited by the presence of live bacteria. Reduced survival during neonatal FFT treatment suggests a potential bioactive attribute of sterile faecal filtrates.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"217 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136033522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hilal Ünsal, Canan Caka, Hacer Neslihan Bildik, Saliha Esenboğa, Alphan Kupesiz, Barış Kuşkonmaz, Duygu Uçkan Cetinkaya, Mirjam van der Burg, İlhan Tezcan, Deniz Çağdaş
{"title":"A large single‐center cohort of bare lymphocyte syndrome: Immunological and genetic features in Turkey","authors":"Hilal Ünsal, Canan Caka, Hacer Neslihan Bildik, Saliha Esenboğa, Alphan Kupesiz, Barış Kuşkonmaz, Duygu Uçkan Cetinkaya, Mirjam van der Burg, İlhan Tezcan, Deniz Çağdaş","doi":"10.1111/sji.13335","DOIUrl":"https://doi.org/10.1111/sji.13335","url":null,"abstract":"Abstract Major histocompatibility complex class II (MHC‐II) deficiency or bare lymphocyte syndrome (BLS) is a rare, early‐onset, autosomal recessive, and life‐threatening inborn error of immunity. We aimed to assess the demographic, clinical, laboratory, follow‐up, and treatment characteristics of patients with MHC‐II deficiency, together with their survival. We retrospectively investigated 21 patients with MHC‐II deficiency. Female/male ratio was 1.63. The median age at diagnosis was 16.3 months (5 months–9.7 years). Nineteen patients (90.5%) had parental consanguinity. Pulmonary diseases (pneumonia, chronic lung disease) (81%), diarrhoea (47.6%), and candidiasis (28.6%) were common. Four (19%) had autoimmunity, two developed septic arthritis, and three (14%) developed bronchiectasis in the follow‐up. Three patients (14%) had CMV viraemia, one with bilateral CMV retinitis. Eight (38.1%) had lymphocytopenia, and four (19%) had neutropenia. Serum IgM, IgA, and IgG levels were low in 18 (85.7%), 15 (71.4%), and 11 (52.4%) patients, respectively. CD4+ lymphocytopenia, a reversed CD4+/CD8+ ratio, and absent/low HLA‐DR expressions were detected in 93.3%, 86.7%, and 100% of the patients, respectively. Haematopoietic stem cell transplantation (HSCT) was performed on nine patients, and four died of septicaemia and ARDS after HSCT. The present median age of patients survived is 14 years (1–31 years). Genetic analysis was performed in 10 patients. RFX5 homozygous gene defect was found in three patients (P1, P4 and P8), and RFXANK (P2 and P14) and RFXAP (P18 and P19) heterozygous gene defects were found in each two patients, respectively. This large cohort showed that BLS patients have severe combined immunodeficiency (SCID)‐like clinical findings. Flow cytometric MHC‐II expression study is crucial for the diagnosis, differential diagnosis with SCID, early haematopoietic stem cell transplantation (HSCT), and post‐HSCT follow‐up. Genetic studies are required first for matched family donor evaluation before HSCT and then for genetic counselling.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"143 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135759488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Charles W. Armitage, Connor P. O'Meara, Emily R. Bryan, Avinash Kollipara, Logan K. Trim, Danica Hickey, Alison J. Carey, Wilhelmina M. Huston, Gavin Donnelly, Anusch Yazdani, Richard S. Blumberg, Kenneth W. Beagley
{"title":"<scp>IgG</scp> exacerbates genital chlamydial pathology in females by enhancing pathogenic <scp>CD8</scp><sup>+</sup> T cell responses","authors":"Charles W. Armitage, Connor P. O'Meara, Emily R. Bryan, Avinash Kollipara, Logan K. Trim, Danica Hickey, Alison J. Carey, Wilhelmina M. Huston, Gavin Donnelly, Anusch Yazdani, Richard S. Blumberg, Kenneth W. Beagley","doi":"10.1111/sji.13331","DOIUrl":"https://doi.org/10.1111/sji.13331","url":null,"abstract":"Abstract Chlamydia trachomatis infections are an important sexually transmitted infection that can lead to inflammation, scarring and hydrosalpinx/infertility. However, infections are commonly clinically asymptomatic and do not receive treatment. The underlying cause of asymptomatic immunopathology remains unknown. Here, we demonstrate that IgG produced during male infection enhanced the incidence of immunopathology and infertility in females. Human endocervical cells expressing the neonatal Fc Receptor (FcRn) increased translocation of human IgG‐opsonized C. trachomatis . Using total IgG purified from infected male mice, we opsonized C. muridarum and then infected female mice, mimicking sexual transmission. Following infection, IgG‐opsonized Chlamydia was found to transcytose the epithelial barrier in the uterus, where it was phagocytosed by antigen‐presenting cells (APCs) and trafficked to the draining lymph nodes. APCs then expanded both CD4 + and CD8 + T cell populations and caused significantly more infertility in female mice infected with non‐opsonized Chlamydia . Enhanced phagocytosis of IgG‐opsonized Chlamydia significantly increased pro‐inflammatory signalling and T cell proliferation. As IgG is transcytosed by FcRn, we utilized FcRn −/− mice and observed that shedding kinetics of Chlamydia were only affected in FcRn −/− mice infected with IgG‐opsonized Chlamydia . Depletion of CD8 + T cells in FcRn −/− mice lead to a significant reduction in the incidence of infertility. Taken together, these data demonstrate that IgG seroconversion during male infection can amplify female immunopathology, dependent on FcRn transcytosis, APC differentiation and enhanced CD8 T cell responses.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"77 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135917847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}