Respiratory Bordetella bronchiseptica Carriage is Associated with Broad Phenotypic Alterations of Peripheral CD4⁺CD25⁺ T Cells and Differentially Affects Immune Responses to Secondary Non-Infectious and Infectious Stimuli in Mice

• Published in: International journal of molecular sciences Vol. 19; no. 9; p. 2602
• Main Authors: Jeron, Andreas, Boehme, Julia D, Volckmar, Julia, Gereke, Marcus, Yevsa, Tetyana, Geffers, Robert, Guzmán, Carlos A, Schreiber, Jens, Stegemann-Koniszewski, Sabine, Bruder, Dunja
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.09.2018; MDPI
• Subjects: Adaptive Immunity - immunology; Animals; Antibodies, Bacterial - blood; Antibodies, Bacterial - immunology; Antigens; Bacteria; Bordetella bronchiseptica; Bordetella bronchiseptica - genetics; Bordetella bronchiseptica - immunology; Bordetella Infections - blood; Bordetella Infections - immunology; Bordetella Infections - microbiology; Bordetella Infections - prevention & control; Carrier State - immunology; Carrier State - microbiology; CD25 antigen; CD4 antigen; CD5 Antigens - analysis; CD8 antigen; Cell activation; Coinfection - blood; Coinfection - immunology; Coinfection - microbiology; Coinfection - prevention & control; Disseminated infection; Foxp3 protein; Immune system; Immunology; Immunoregulation; Influenza; Influenza A; influenza A virus; Influenza A virus - genetics; Influenza A virus - immunology; Laboratory animals; Lactobacillus plantarum; Leukocytes; Listeria; Listeria monocytogenes; Listeria monocytogenes - genetics; Listeria monocytogenes - immunology; Lungs; Lymphocytes; Lymphocytes T; Mice; Mice, Inbred BALB C; Microorganisms; polymicrobial interactions; regulatory T cells; respiratory immune regulation; respiratory microbial carriage; Respiratory tract; Respiratory Tract Infections - blood; Respiratory Tract Infections - immunology; Respiratory Tract Infections - prevention & control; secondary infections; Streptococcus infections; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - microbiology; Transcription activation; Vaccination; Whooping cough; Germany; regulatory T cells; Bordetella bronchiseptica; respiratory immune regulation; secondary infections; polymicrobial interactions; Listeria monocytogenes; respiratory microbial carriage; influenza A virus; vaccination
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19092602

The respiratory tract is constantly exposed to the environment and displays a favorable niche for colonizing microorganisms. However, the effects of respiratory bacterial carriage on the immune system and its implications for secondary responses remain largely unclear. We have employed respiratory carriage with as the underlying model to comprehensively address effects on subsequent immune responses. Carriage was associated with the stimulation of -specific CD4⁺, CD8⁺, and CD4⁺CD25⁺Foxp3⁺ T cell responses, and broad transcriptional activation was observed in CD4⁺CD25⁺ T cells. Importantly, transfer of leukocytes from carriers to acutely infected mice, resulted in a significantly increased bacterial burden in the recipient's upper respiratory tract. In contrast, we found that respiratory carriage resulted in a significant benefit for the host in systemic infection with Adaptive responses to vaccination and influenza A virus infection, were unaffected by carriage. These data showed that there were significant immune modulatory processes triggered by carriage, that differentially affect subsequent immune responses. Therefore, our results demonstrated the complexity of immune regulation induced by respiratory bacterial carriage, which can be beneficial or detrimental to the host, depending on the pathogen and the considered compartment.