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Toll‐like receptor 4 is not required for the full maturation of dendritic cells or for the degradation of Gram‐negative bacteria

Toll‐like receptor 4 (TLR4) has been recently associated with cellular responses to lipopolysaccharide (LPS), and mice mutated in tlr4, such as C57BL/10ScCr or C3H/HeJ mice, become hyporesponsive to LPS. In this study, we have analyzed the capacity of bone marrow‐derived dendritic cells (BMDC) from C57BL/10ScCr (ScCr‐BMDC) or C3H/HeJ (HeJ‐BMDC) mice to respond to LPS or to Gram‐negative bacteria. We show that ScCr‐ or HeJ‐BMDC are insensitive to LPS, but can mature in response to live and killed Gram‐negative bacteria. Interestingly, only ScCr‐BMDC but not HeJ‐BMDC, stimulated with bacteria, have reduced capacity to produce pro‐ and anti‐inflammatory cytokines as compared to BMDC from control mice, probably due to genetic defects unrelated to the tlr4 mutation. Nevertheless, ScCr‐BMDC and ScCr BM‐macrophages (BM‐Mϕ) phagocytose Salmonella typhimurium similarly to control cells, indicating that TLR4 is not compulsory for bacterial uptake. Moreover, BM‐Mϕ, but not BM‐DC from B10ScCr or C3H/HeJ mice, are impaired in their capacity to kill intracellular bacteria and to produce NO as compared to wild type controls. However, the bacteria killing property of BM‐Mϕ is completely restored by pretreating the cells with IFN‐γ. Hence, TLR4 plays different roles in DC versus Mϕ.