SND1 promotes Th1/17 immunity against chlamydial lung infection through enhancing dendritic cell function
Autor: | Chunyan Zhang, Shuhe Wang, Xinting Wang, Jie Yang, Rony Thomas, Xi Yang, Rasheduzzaman Rashu |
---|---|
Rok vydání: | 2021 |
Předmět: |
Adoptive cell transfer
Physiology Cell Chlamydia Infection White Blood Cells Mice Medical Conditions 0302 clinical medicine Animal Cells Immune Physiology Medicine and Health Sciences Biology (General) Immune Response Lung Staining Mice Knockout Innate Immune System Immunity Cellular 0303 health sciences biology T Cells Cell Staining FOXP3 Animal Models 3. Good health Infectious Diseases medicine.anatomical_structure Experimental Organism Systems Cytokines Female Cellular Types Intracellular Research Article Chlamydia muridarum QH301-705.5 Immune Cells Immunology Sexually Transmitted Diseases Cytotoxic T cells Mouse Models Research and Analysis Methods Microbiology 03 medical and health sciences Model Organisms Immune system Immunity Virology Genetics medicine Animals Molecular Biology 030304 developmental biology Blood Cells Biology and Life Sciences Cell Biology Dendritic Cells Dendritic cell RC581-607 Molecular Development Chlamydia Infections Th1 Cells Endonucleases biology.organism_classification Mice Inbred C57BL Specimen Preparation and Treatment Immune System Animal Studies Th17 Cells Parasitology Immunologic diseases. Allergy Spleen Developmental Biology 030215 immunology |
Zdroj: | PLoS Pathogens PLoS Pathogens, Vol 17, Iss 2, p e1009295 (2021) |
ISSN: | 1553-7374 |
Popis: | To date, no reports have linked the multifunctional protein, staphylococcal nuclease domain-containing protein 1 (SND1), to host defense against intracellular infections. In this study, we investigated the role and mechanisms of SND1, by using SND1 knockout (SND1-/-) mice, in host defense against the lung infection of Chlamydia muridarum, an obligate intracellular bacterium. Our data showed that SND1-/- mice exhibited significantly greater body weight loss, higher organism growth, and more severe pathological changes compared with wild-type mice following the infection. Further analysis showed significantly reduced Chlamydia-specific Th1/17 immune responses in SND1-/- mice after infection. Interestingly, the dendritic cells (DCs) isolated from SND1-/- mice showed lower costimulatory molecules expression and IL-12 production, but higher IL-10 production compared with those from wild-type control mice. In the DC-T cell co-culture system, DCs isolated from SND1-/- infected mice showed significantly reduced ability to promote Chlamydia-specific IFN-γ producing Th1 cells but enhanced capacity to induce CD4+T cells into Foxp3+ Treg cells. Adoptive transfer of DCs isolated from SND1-/- mice, unlike those from wild-type control mice, failed to protect the recipients against challenge infection. These findings provide in vivo evidence that SND1 plays an important role in host defense against intracellular bacterial infection, and suggest that SND1 can promote Th1/17 immunity and inhibit the expansion of Treg cells through modulation of the function of DCs. Author summary Since the initial study from our group reported that SND1 is able to hijack nascent MHC-I heavy chain in tumor cells, thereby impairing the proper assembling of MHC-I and sensitizing tumor cells to a diminished immune surveillance with abolished antigen presentation to cytotoxic CD8+ T cells, large attention has been drawn to its importance in host immunity. To date, no reports have been linked SND1 to immune response against bacterial infection. In this study, we investigated the role and mechanisms of SND1 in chlamydial lung infection by using SND1 knockout mice. We found that SND1 knockout mice showed significantly delayed clearance of bacteria and more severe disease. More importantly, we found that the SND1 deficiency led to alteration of phenotype and function of dendritic cells, which is associated with a failure in the development of protective Th1/17 immunity. These data indicate that SND1 protein plays an important role in host defense against chlamydial infection, at least partially through modulating dendritic cell function. |
Databáze: | OpenAIRE |
Externí odkaz: |