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-Mphi) phagocytose Salmonella typhimurium similarly to control cells, indicating that TLR4 is not compulsory for bacterial uptake. Moreover, BM-Mphi, 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-Mphi is completely restored by pretreating the cells with IFN-gamma. Hence, TLR4 plays different roles in DC versus Mphi.
Toll-like receptor 4 is not required for the full maturation of dendritic cells or for the degradation of Gram-negative bacteria / M. Rescigno, M. Urbano, M. Rimoldi, B. Valzasina, G. Rotta, F. Granucci, P. Ricciardi-Castagnoli. - In: EUROPEAN JOURNAL OF IMMUNOLOGY. - ISSN 0014-2980. - 32:10(2002 Oct), pp. 2800-2806. [10.1002/1521-4141(2002010)32:10<2800::AID-IMMU2800>3.0.CO;2-5]
Toll-like receptor 4 is not required for the full maturation of dendritic cells or for the degradation of Gram-negative bacteria
M. RescignoPrimo
;
2002
Abstract
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-Mphi) phagocytose Salmonella typhimurium similarly to control cells, indicating that TLR4 is not compulsory for bacterial uptake. Moreover, BM-Mphi, 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-Mphi is completely restored by pretreating the cells with IFN-gamma. Hence, TLR4 plays different roles in DC versus Mphi.File | Dimensione | Formato | |
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