The Campylobacter jejuni NCTC11168 capsule prevents excessive cytokine production by dendritic cells

Campylobacter jejuni is the leading cause of human bacterial gastroenteritis worldwide, mainly caused by handling and consumption of contaminated poultry. However, the immune response to infection is poorly understood. Here, the impact of the C. jejuni capsule, flagella and the N-linked glycosylation system on cytokine production by dendritic cells was investigated. Bone marrow-derived murine dendritic cells (BMDCs) infected with C. jejuni lacking the N-linked glycosylation system produced similar amounts of cytokines compared to cells infected with C. jejuni 11168H wild-type (WT) cultures. C. jejuni flagellin FlaA mutants elicited reduced IL-6 and IL-10 production in BMDCs compared to C. jejuni WT and this reduction was more pronounced in TLR4(-/-) BMDCs. An acapsular C. jejuni mutant as well as a mutant lacking the O-methyl phosphoramidate modification of the capsule elicited a higher cytokine response in BMDCs. Experiments with TLR4(-/-) BMDCs revealed that this increased cytokine production was not solely dependent on signalling through TLR4. Therefore, the C. jejuni capsule is important to prevent excessive cytokine production by BMDCs and even minor changes in capsule composition such as the lack of the O-methyl phosphoramidate modification can lead to increased cytokine production.