TLR7 trafficking and signaling in B cells is regulated by the MHCII-associated invariant chain

J Cell Sci. 2020 Mar 10;133(5):jcs236711. doi: 10.1242/jcs.236711.

Abstract

Toll-like receptor 7 (TLR7) is an endosomal receptor that recognizes single-stranded RNA from viruses. Its trafficking and activation is regulated by the endoplasmic reticulum (ER) chaperone UNC93B1 and lysosomal proteases. UNC93B1 also modulates major histocompatibility complex class II (MHCII) antigen presentation, and deficiency in MHCII protein diminishes TLR9 signaling. These results indicate a link between proteins that regulate both innate and adaptive responses. Here, we report that TLR7 resides in lysosomes and interacts with the MHCII-chaperone molecule, the invariant chain (Ii) or CD74, in B cells. In the absence of CD74, TLR7 displays both ER and lysosomal localization, leading to an increase in pro-inflammatory cytokine production. Furthermore, stimulation with TLR7 but not TLR9, is inefficient in boosting antigen presentation in Ii-deficient cells. In contrast, in B cells lacking TLR7 or mutated for UNC93B1, which are able to trigger TLR7 activation, antigen presentation is enhanced. This suggests that TLR7 signaling in B cells is controlled by the Ii chain.

Keywords: B cells; Invariant chain; Toll-like receptor 7; UNC93B1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Differentiation, B-Lymphocyte / genetics
  • B-Lymphocytes / metabolism
  • Histocompatibility Antigens Class II
  • Membrane Transport Proteins*
  • Toll-Like Receptor 7* / genetics
  • Toll-Like Receptor 7* / metabolism

Substances

  • Antigens, Differentiation, B-Lymphocyte
  • Histocompatibility Antigens Class II
  • Membrane Transport Proteins
  • Toll-Like Receptor 7
  • invariant chain