Profiling of innate and adaptive immune cells during influenza virus infection reveals sex bias in invariant natural killer T (iNKT) cells
Abstract Background Influenza A virus (IAV) infection leads to significant morbidity and mortality. Biological sex influences the immune responses to IAV infection, resulting in higher mortality in women of reproductive age. Previous studies revealed increased activation of T and B cells in female m...
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| Format: | Article |
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Wiley
2023-04-01
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| Series: | Immunity, Inflammation and Disease |
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| Online Access: | https://doi.org/10.1002/iid3.837 |
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| author | Piotr Humeniuk Aidan Barrett Hannes Axelsson Carmen Corciulo Christina Drevinge Alicia Del Carpio Pons Davide Angeletti Julia M. Scheffler Ulrika Islander |
| author_facet | Piotr Humeniuk Aidan Barrett Hannes Axelsson Carmen Corciulo Christina Drevinge Alicia Del Carpio Pons Davide Angeletti Julia M. Scheffler Ulrika Islander |
| author_sort | Piotr Humeniuk |
| collection | DOAJ |
| description | Abstract Background Influenza A virus (IAV) infection leads to significant morbidity and mortality. Biological sex influences the immune responses to IAV infection, resulting in higher mortality in women of reproductive age. Previous studies revealed increased activation of T and B cells in female mice after IAV infection, but extensive analysis of sex differences in both innate and adaptive immune cells over time is lacking. Invariant natural killer T (iNKT) cells are fast‐reacting forces and modulators of immune responses that are important to IAV immunity, but it is not known if the presence and function of iNKT cells differ between females and males. The aim of this study was to determine immunological mechanisms that contribute to the increased disease severity in female mice during IAV infection. Methods Female and male mice were infected with mouse‐adapted IAV and monitored for weight loss and survival. Immune cell populations and cytokine expression in bronchoalveolar lavage fluid, lung, and mediastinal lymph node were determined at three time points after infection using flow cytometry and ELISA. Results The results reveal increased severity and mortality in adult female mice compared to age‐matched males. Female mice show larger increases in innate and adaptive immune cell populations and cytokine production in lung compared to mock on Day 6 postinfection. On Day 9 postinfection, female mice express higher numbers of iNKT cells in lung and liver compared to males. Conclusions This comprehensive analysis of immune cells and cytokines over time following IAV infection reveals increased leukocyte expansion and stronger proinflammatory cytokine responses in female mice during disease initiation. Furthermore, this is the first study to report a sex bias in iNKT cell populations after IAV infection. The data suggests that the process of recovery from IAV‐induced airway inflammation is associated with increased expansion of several different iNKT cell subpopulations in female mice. |
| format | Article |
| id | doaj-art-efaa3f4b914b4a5db78cb8a77ceb91f7 |
| institution | DOAJ |
| issn | 2050-4527 |
| language | English |
| publishDate | 2023-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Immunity, Inflammation and Disease |
| spelling | doaj-art-efaa3f4b914b4a5db78cb8a77ceb91f72025-08-20T03:06:26ZengWileyImmunity, Inflammation and Disease2050-45272023-04-01114n/an/a10.1002/iid3.837Profiling of innate and adaptive immune cells during influenza virus infection reveals sex bias in invariant natural killer T (iNKT) cellsPiotr Humeniuk0Aidan Barrett1Hannes Axelsson2Carmen Corciulo3Christina Drevinge4Alicia Del Carpio Pons5Davide Angeletti6Julia M. Scheffler7Ulrika Islander8Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy University of Gothenburg Gothenburg SwedenDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy University of Gothenburg Gothenburg SwedenDepartment of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy University of Gothenburg Gothenburg SwedenDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy University of Gothenburg Gothenburg SwedenDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy University of Gothenburg Gothenburg SwedenDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy University of Gothenburg Gothenburg SwedenDepartment of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy University of Gothenburg Gothenburg SwedenDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy University of Gothenburg Gothenburg SwedenDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy University of Gothenburg Gothenburg SwedenAbstract Background Influenza A virus (IAV) infection leads to significant morbidity and mortality. Biological sex influences the immune responses to IAV infection, resulting in higher mortality in women of reproductive age. Previous studies revealed increased activation of T and B cells in female mice after IAV infection, but extensive analysis of sex differences in both innate and adaptive immune cells over time is lacking. Invariant natural killer T (iNKT) cells are fast‐reacting forces and modulators of immune responses that are important to IAV immunity, but it is not known if the presence and function of iNKT cells differ between females and males. The aim of this study was to determine immunological mechanisms that contribute to the increased disease severity in female mice during IAV infection. Methods Female and male mice were infected with mouse‐adapted IAV and monitored for weight loss and survival. Immune cell populations and cytokine expression in bronchoalveolar lavage fluid, lung, and mediastinal lymph node were determined at three time points after infection using flow cytometry and ELISA. Results The results reveal increased severity and mortality in adult female mice compared to age‐matched males. Female mice show larger increases in innate and adaptive immune cell populations and cytokine production in lung compared to mock on Day 6 postinfection. On Day 9 postinfection, female mice express higher numbers of iNKT cells in lung and liver compared to males. Conclusions This comprehensive analysis of immune cells and cytokines over time following IAV infection reveals increased leukocyte expansion and stronger proinflammatory cytokine responses in female mice during disease initiation. Furthermore, this is the first study to report a sex bias in iNKT cell populations after IAV infection. The data suggests that the process of recovery from IAV‐induced airway inflammation is associated with increased expansion of several different iNKT cell subpopulations in female mice.https://doi.org/10.1002/iid3.837airway inflammationinfectioninfluenza A virusinvariant natural killer T (iNKT) cellslymphocytesmyeloid cells |
| spellingShingle | Piotr Humeniuk Aidan Barrett Hannes Axelsson Carmen Corciulo Christina Drevinge Alicia Del Carpio Pons Davide Angeletti Julia M. Scheffler Ulrika Islander Profiling of innate and adaptive immune cells during influenza virus infection reveals sex bias in invariant natural killer T (iNKT) cells Immunity, Inflammation and Disease airway inflammation infection influenza A virus invariant natural killer T (iNKT) cells lymphocytes myeloid cells |
| title | Profiling of innate and adaptive immune cells during influenza virus infection reveals sex bias in invariant natural killer T (iNKT) cells |
| title_full | Profiling of innate and adaptive immune cells during influenza virus infection reveals sex bias in invariant natural killer T (iNKT) cells |
| title_fullStr | Profiling of innate and adaptive immune cells during influenza virus infection reveals sex bias in invariant natural killer T (iNKT) cells |
| title_full_unstemmed | Profiling of innate and adaptive immune cells during influenza virus infection reveals sex bias in invariant natural killer T (iNKT) cells |
| title_short | Profiling of innate and adaptive immune cells during influenza virus infection reveals sex bias in invariant natural killer T (iNKT) cells |
| title_sort | profiling of innate and adaptive immune cells during influenza virus infection reveals sex bias in invariant natural killer t inkt cells |
| topic | airway inflammation infection influenza A virus invariant natural killer T (iNKT) cells lymphocytes myeloid cells |
| url | https://doi.org/10.1002/iid3.837 |
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