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
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