TY - JOUR
T1 - Toll-like receptor 4 is not required for the full maturation of dendritic cells or for the degradation of Gram-negative bacteria
AU - Rescigno, Maria
AU - Urbano, Matteo
AU - Rimoldi, Monica
AU - Valzasina, Barbara
AU - Rotta, Gianluca
AU - Granucci, Francesca
AU - Ricciardi-Castagnoli, Paola
PY - 2002/10
Y1 - 2002/10
N2 - 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.
AB - 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.
KW - Dendritic cell
KW - LPS
KW - Nitric oxide
KW - Salmonella typhimurium
KW - TLR4
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U2 - 10.1002/1521-4141(2002010)32:10<2800::AID-IMMU2800>3.0.CO;2-5
DO - 10.1002/1521-4141(2002010)32:10<2800::AID-IMMU2800>3.0.CO;2-5
M3 - Article
C2 - 12355432
AN - SCOPUS:0036772290
VL - 32
SP - 2800
EP - 2806
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 10
ER -