Infection of C57BL/10ScCr and C57BL/10ScNCr mice with Leishmania major reveals a role for Toll-like receptor 4 in the control of parasite replication.
The innate immune system is essential for host defense; it senses the presence of potentially pathogenic-invading microorganisms, and the contribution of Toll-like receptors (TLRs) to this response is increasingly recognized. In the present study, we investigated the contribution of TLR4 to the course of cutaneous leishmaniasis in vivo. We used C57BL/10ScNCr (TLR4(0/0)) and C57BL/10ScCr [TLR4/interleukin-12 (IL-12)Rbeta2(0/0)] mice and compared the course of Leishmania major infection, parasite load, cell recruitment, and cytokine profile with those of wild-type C57BL/10ScSn mice. Our results confirm the importance of IL-12 receptor-mediated signaling in resistance to L. major infections. Importantly, we show that the lack of TLR4 results in an increased permissiveness for parasite growth during the innate and adaptive phase of the immune response and in delayed healing of the cutaneous lesions. The use of the tlr4 transgenic mouse strain TCr5 demonstrated unequivocally that TLR4 contributes to the efficient control of Leishmania growth in vivo.
Kropf
P
P
Faculty of Medicine, Division of Investigative Science, Department of Immunology, Norfolk Place, London, W2 1PG, United Kingdom.
Freudenberg
N
N
Kalis
C
C
Modolell
M
M
Herath
S
S
Galanos
C
C
Freudenberg
M
M
Müller
I
I
D000818:Animals; D018320:Leishmania major / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000276:immunology*; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology*; D053707:Receptors, Interleukin-12; D012867:Skin / Q000469:parasitology* / Q000473:pathology; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors