Seminar - Intestinal dendritic cell subset specification and their role during infection

THE UNIVERSITY OF BRITISH COLUMBIA
Department of Microbiology and Immunology
presents a seminar by:
Dr. Katharina Lahl
Associate Professor, Lund University, Department of Experimental Medical Sciences, Immunology Section
entitled:
Seminar - Intestinal dendritic cell subset specification and their role during infection



Sponsored by: The Department of Microbiology and Immunology

Please note, this seminar will be Hybrid (in-person & Zoom). The seminar will be in LSC3 but if you prefer to join via Zoom, please join with the meeting ID & Passcode sent in the M&I email or email parvin@mail.ubc.ca for how to join! 
 



Abstract: Dendritic cells (DCs) are unique in their ability to present antigen to naïve adaptive immune cells and thereby are playing key roles in the initiation of antigen-specific immunity. Classical DCs are broadly grouped into two subsets, which differ in their ability to activate in response to specific triggers and their preference of imprinting flavors of immunity. cDC1 are associated with the response to viruses and intracellular bacteria and are powerful coordinators of type 1 immunity, while cDC2 are thought to induce type 2 and type 17 responses towards parasites, fungi and extracellular bacteria. Humoral immunity was shown to be mainly driven by cDC2, but this has been studied primarily in the context of extracellular bacterial infections and steady state immunity to commensals, triggers known to preferentially engage the cDC2 subset. Using our murine model of Rotavirus infection to assess the role of intestinal DC subsets in the initiation of adaptive immunity towards enteric viruses, we found that cDC1 drive adaptive immunity towards Rotavirus, including the initiation of optimal IgA response at the mucosal surface. IgA induction by cDC1 depended on their expression of the integrin a4b7, providing bioactive TGFb. This work shows that cDC1 can induce IgA in the context of a viral infection.

Our interest in the role of DC subsets in inducing humoral immunity led us to analyze the role of the transcription factor Bcl6 in DC subset biology, as Bcl6 is crucial for germinal center reactions, and we previously found that Bcl6 is expressed in DCs. We found that cDC1 do not depend on Bcl6 per se but present with a partial gain of a cDC2-associated phenotype. In contrast, the lack of Bcl6 in cDC2 leads to a partial loss of this subset, reminiscent of the phenotype observed in cDC-specific Notch2-deficient mice. Accordingly, mice harboring a cDC-specific Bcl6 deficiency fail at mounting optimal germinal center responses to particulate blood-derived antigen and Th17 responses upon infection with Citrobacter rodentium. Our findings establish Bcl6 as an essential transcription factor for a subset of cDC2 and add to our understanding of the transcriptional landscape underlying cDC2 heterogeneity.

Thursday, March 10, 2022 - 11:00am to 12:00pm

Location:
Life Sciences Centre, LSC 3
2350 Health Sciences Mall
Hosted by
Dr. Maria Tokuyama