Characterization of IL-10-producing B cells and their suppressive activities during primary and secondary Salmonella typhimurium infection

• Applicant: Professor Dr. Simon Fillatreau
• Subject Area: Immunology
• Term: from 2009 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 116594012

The immune system is essential for protection from infections. It senses invading pathogens via receptors, such as Toll-like receptors (TLR), that detect conserved molecules expressed by entire classes of microbes but possess only minimal reactivity against healthy tissues. These receptors control the activation of immune cells, and they have determinant roles on the progression of immune responses. Deficiencies in TLR signalling can lead to severe immunodeficiencies. In keeping with the strong immune activating properties of TLRs, synthetic agonists of these receptors are currently being tested in the clinic as adjuvant to improve vaccines against cancer or infectious diseases. Multiple cell types express TLRs, but the contribution of each cell type to the effects induced by TLR agonists is poorly understood. We have recently identified a unique regulatory function for TLR-activated B cells, by showing that TLR-signalling in B cells can result in suppression of immunity and resolution of an autoimmune disease. These preliminary results suggest that TLR-activated B cells can interfere with immune defence against some microbes and hinder the functions of particular microbial adjuvant. On the other hand, TLR-signalling in B cells may also be essential for the development of a long-lived humoral immunity - a key protective mechanism for many vaccines. This proposal will extend our preliminary findings to test how TLR-triggering in B cells influences immunity to Salmonella typhimurium, on one hand, and the adjuvant functions of purified TLR agonists, on another. At the end of the project, we should be able to determine whether manipulating the B cell system through TLRs can be used to strengthen host protection against microbes and to improve vaccines efficacy.

• DFG Programme: Research Grants