Microbiota regulate the ability of lung dendritic cells to induce IgA class-switch recombination and generate protective gastrointestinal immune responses

Autor: Aakash Garg, Haekyung Lee, Michael A. Oropallo, Jeremiah J. Faith, Noa Simchoni, Gaurav Pandey, Michelle Gaylord, Charlotte Cunningham-Rundles, Adeeb Rahman, Miriam Merad, Konstantina Alexandropoulos, Meimei Shan, Andrea Cerutti, Ryan C. Ungaro, Daniel Mucida, Alejo Chorny, Darren Ruane, Erica G. Weinstein, Saurabh Mehandru
Rok vydání: 2015
Předmět:
0301 basic medicine
Immunoglobulin A
Integrins
Tumor Necrosis Factor Ligand Superfamily Member 13
Immunology
Gene Expression
Tretinoin
medicine.disease_cause
Article
Mice
Receptors
CCR
03 medical and health sciences
0302 clinical medicine
Immune system
Antigen
Antigens
CD
Cell Movement
Transforming Growth Factor beta
B-Cell Activating Factor
Macrophages
Alveolar
medicine
Animals
Immunology and Allergy
Receptor
B-cell activating factor
Lung
Research Articles
B-Lymphocytes
biology
Microbiota
Cholera toxin
CD24 Antigen
Dendritic Cells
Transforming growth factor beta
Immunoglobulin Class Switching
3. Good health
Gastrointestinal Tract
Adaptor Proteins
Vesicular Transport
030104 developmental biology
Immunoglobulin class switching
Myeloid Differentiation Factor 88
biology.protein
Integrin alpha Chains
030215 immunology
Zdroj: The Journal of Experimental Medicine
ISSN: 1540-9538
0022-1007
DOI: 10.1084/jem.20150567
Popis: Ruane et al. demonstrate a role for the microbiota in modulating protective immunity to intranasal vaccination via the ability of lung dendritic cells to induce B cell IgA class switching.
Protective immunoglobulin A (IgA) responses to oral antigens are usually orchestrated by gut dendritic cells (DCs). Here, we show that lung CD103+ and CD24+CD11b+ DCs induced IgA class-switch recombination (CSR) by activating B cells through T cell–dependent or –independent pathways. Compared with lung DCs (LDC), lung CD64+ macrophages had decreased expression of B cell activation genes and induced significantly less IgA production. Microbial stimuli, acting through Toll-like receptors, induced transforming growth factor-β (TGF-β) production by LDCs and exerted a profound influence on LDC-mediated IgA CSR. After intranasal immunization with inactive cholera toxin (CT), LDCs stimulated retinoic acid–dependent up-regulation of α4β7 and CCR9 gut-homing receptors on local IgA-expressing B cells. Migration of these B cells to the gut resulted in IgA-mediated protection against an oral challenge with active CT. However, in germ-free mice, the levels of LDC-induced, CT–specific IgA in the gut are significantly reduced. Herein, we demonstrate an unexpected role of the microbiota in modulating the protective efficacy of intranasal vaccination through their effect on the IgA class-switching function of LDCs.
Databáze: OpenAIRE
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