In susceptible mice, Leishmania major induce very rapid interleukin‐4 production by CD4+ T cells which are NK1.1−

Launois, Pascal; Ohteki, Toshiaki; Swihart, Kristin G.; MacDonald, H. Robson; Louis, J A

doi:10.1002/eji.1830251215

Cited by 155 publications

(157 citation statements)

References 62 publications

Supporting

Mentioning

148

Contrasting

Unclassified

Order By: Relevance

“…This is in contrast to previously published observations made in the murine model using subcutaneous infection in the footpad, where a rapid and intense production of IL-4 was detected in the draining lymph nodes of BALB/c mice but not mice of resistant strains. 17,22,23 In addition, although cytokine producing cells were detected in the skin at 24 h by immunohistochemistry, a similar number of IL-4 producing cells was observed in both C57BL/6 and BALB/c mice. The discrepancy in the early IL-4 production may be related to the different model of infection used, since there is evidence that the route of infection may lead to different disease phenotypes and different cytokine profiles.…”

Section: Discussionmentioning

confidence: 85%

“…The data obtained in the footpad model 17 indicated that a strong increase in IL-4 production during the first 24 h after infection of the susceptible BALB/c mice was the cause of the inability of these mice to cure infection. Therefore, expression of IL-4 and IFN-g mRNA in the draining lymph nodes was measured at 8, 16 and 24 h postinfection.…”

Section: Expression Of Mrna For Selected Cytokines and Cytokine Recepmentioning

confidence: 99%

See 1 more Smart Citation

Dissociation of disease susceptibility, inflammation and cytokine profile in lmr1/2 congenic mice infected with Leishmania major

et al. 2004

View full text Add to dashboard Cite

Severity of disease caused by Leishmania major depends on the genetics of the host. Early induction of T helper cell type 1 (Th1)-type responses in resistant C57BL/6 mice and T helper cell type 2 (Th2) in susceptible BALB/c mice is thought to determine cure or disease respectively. We have mapped three loci that confer susceptibility or resistance upon congenic mice on the C57BL/6 or BALB/c backgrounds. Here we examine the histopathology and production of interleukin 4 (IL-4) and interferon gamma (IFN-g) in the skin and draining lymph nodes in the congenic and parental mice. We show an evolving granuloma with a staged infiltration of inflammatory cells, but no difference between the groups. As an indication of an earlypolarised Th1/Th2 response we measured IFN-g and IL-4 in the lymph nodes and found no difference between any of the mice during the first 48 h. During infection, the level of IL-4 correlated with the lesion size, indicating that IL-4 reflects the disease severity rather than controls it. Considering this effect, B6.C(lmr1,lmr2) mice had similar cytokine levels to the parental C57BL/ 6 mice despite increased susceptibility and C.B6(lmr1,lmr2) were similar to BALB/c despite increased resistance. We conclude that the lmr loci affect disease severity by a mechanism independent of conventional helper T-cell responses. Genes and Immunity (2004) IntroductionThe first demonstration that the balance of T helper cell responses determines the severity of the pathology in an infectious disease model came from studies on murine cutaneous leishmaniasis caused by infection with Leishmania major. A large number of studies have shown that susceptibility to disease in BALB/c mice correlated with the dominance of interleukin 4 (IL-4)-driven T helper cell type 2 (Th2)-type responses, while resistance in C57BL/6 mice correlated with the dominance of interferon gamma (IFN-g)-driven T helper cell type 1 (Th1) responses. 1,2 However, as pointed out by Sacks and Noben-Trauth, 3 the simplicity of this model has begun to be challenged. For example, there are data indicating that IL-4 is not sufficient to mediate progressive disease, 4 nor is it essential for the induction of Th2 responses 5 and ablation of IL-4 or IL-4 signaling in BALB/c mice does not necessarily lead to resistance. 6 Studies are underway in many laboratories to map the genes that determine susceptibility to leishmaniasis in the expectation that they may help identify mechanisms of polarisation of the T helper cell responses. Although linkage to L. major response phenotypes has been mapped to loci on chromosomes 5, 6, 9, 10, 11, 15, 17 and X, 7-11 the relationship between these loci and the control of the polarisation of T cell responses in response to L. major has not been determined.We used a genome-wide scan on two large populations of F2 mice created from a cross between the susceptible BALB/c and the resistant C57BL/6 strains, and showed that susceptibility to disease caused by intradermal infection at the base of the tail with L. major is controlle...

show abstract

Section: Discussionmentioning

confidence: 85%

Section: Expression Of Mrna For Selected Cytokines and Cytokine Recepmentioning

confidence: 99%

Dissociation of disease susceptibility, inflammation and cytokine profile in lmr1/2 congenic mice infected with Leishmania major

et al. 2004

View full text Add to dashboard Cite

show abstract

“…Several experimental results also strongly support a requisite role of IL-4 in mediating both Th2 cell differentiation and susceptibility to L. major in BALB/c mice (11,12). In this context, prior studies from this laboratory have shown that susceptible BALB/c mice, in contrast to mice from resistant strains, exhibited a burst of IL-4 mRNA expression in CD4 ϩ T cells from the draining lymph nodes (LN) within 1 day after infection with L. major (13). This early burst of IL-4 expression occurred in a restricted population of V␤4-V␣8 CD4 ϩ T cells after cognate recognition of a single epitope of the Leishmania homologue (LACK) 4 (14) of mammalian RACK1 (15).…”

Section: In Balb/c Mice Il-4 Production During the Initial Phase Of mentioning

confidence: 79%

In BALB/c Mice, IL-4 Production During the Initial Phase of Infection withLeishmania majorIs Necessary and Sufficient to Instruct Th2 Cell Development Resulting in Progressive Disease

Himmelrich

Launois

Maillard

et al. 2000

The Journal of Immunology

Self Cite

116

105

View full text Add to dashboard Cite

In contrast to intact BALB/c mice, BALB/c mice rendered deficient in Vβ4+ CD4+ T cells develop a Th1 response to infection with Leishmania major and are resistant. Vβ4-deficient BALB/c mice are unable to generate the early IL-4 transcription occurring in Vβ4 Vα8 CD4+ T cells of BALB/c mice within 1 day of infection. Here we demonstrate that treatment of Vβ4-deficient BALB/c mice with IL-4 during the first 64 h after infection instructs Th2 cell development and susceptibility to infection. The demonstrated inability of IL-4 to reverse the resistant phenotype of BALB/c mice treated with anti-CD4 mAb the day before infection suggest that these effects of IL-4 require its interaction with CD4+ T cells. In contrast to draining lymph node cells from BALB/c mice, cells from Vβ4-deficient BALB/c mice remain responsive to IL-12 following infection. Strikingly, administration of IL-4 to Vβ4-deficient BALB/c mice renders their lymph node cells unresponsive to IL-12 by down-regulating IL-12R β2-chain expression. This study directly demonstrates that in BALB/c mice IL-4 is necessary and sufficient to initiate the molecular events steering Th2 cell maturation and susceptibility to L. major.

show abstract

“…The Relative Contribution of IL-4 Receptor Signaling and IL-10 to Susceptibility to Leishmania major 1 Nancy Noben-Trauth, 2 * Rosalia Lira, 3 A cquired resistance to Leishmania major is associated with the development of a Th1-dominated response, with IFN-␥ as the key effector cytokine able to activate macrophages to kill intracellular parasites. In contrast, susceptibility to L. major has been attributed to a Th2 response dominated by high levels of IL-4 and low amounts of IFN-␥, establishing this as the prototypic model to study polarized Th2 responses in vivo (1,2).…”

mentioning

confidence: 99%

“…In contrast, susceptibility to L. major has been attributed to a Th2 response dominated by high levels of IL-4 and low amounts of IFN-␥, establishing this as the prototypic model to study polarized Th2 responses in vivo (1,2). In BALB/c mice, L. major is able to stimulate a burst of IL-4 production in the draining lymph node (LN) 4 as early as 16 h following s.c. infection (3). Much of the early IL-4 is thought to derive from an oligoclonal population of CD4 ϩ T cells with the V␤4 V␣8 TCR that recognize the Leishmania Ag Leishmania homolog of receptors for activated C kinase (4,5).…”

mentioning

confidence: 99%

The Relative Contribution of IL-4 Receptor Signaling and IL-10 to Susceptibility toLeishmania major

Noben-Trauth

Lira²,

Nagase

et al. 2003

The Journal of Immunology

113

101

View full text Add to dashboard Cite

The roles of IL-10 and IL-4 receptor signaling were evaluated in a murine model of Leishmania major infection. In previous studies the L. major substrain LV39 caused progressive, nonhealing lesions in BALB/c mice deficient for IL-4R α-chain (IL-4Rα), while substrain IR173 was highly controlled. To explore whether IL-10 is responsible for inducing susceptibility to LV39, wild-type and IL-4Rα−/− mice were treated with anti-IL-10R mAb, and in a genetic approach, the IL-4Rα−/− mice were crossed with BALB/c IL-10−/− mice. In contrast to the lack of resistance conferred by IL-4Rα gene deletion, partial resistance to LV39 was conferred by IL-10 gene deletion or treatment of BALB/c mice with anti-IL-10R mAb. Lesion sizes and LV39 parasite numbers were further and dramatically reduced in both anti-IL-10R-treated IL-4Rα−/− mice and IL-4Rα × IL-10 double knockouts. Anti-IL-10R mAb treatment further suppressed parasite growth in IL-4Rα−/− mice infected with L. major IR173. Production of IFN-γ was only increased relative to wild-type or littermate controls in IL-4Rα−/− mice with complementary defects in IL-10. Comparisons of IFN-γ-treated infected macrophages in vitro indicated that LV39 required 25- to 500-fold greater concentrations of IFN-γ than IR173-infected macrophages to achieve a similar efficiency of parasite killing. These studies suggest that regardless of parasite substrain, IL-10 is as important as IL-4/IL-13 in promoting susceptibility to L. major and even more so for those substrains that are relatively resistant to IFN-γ mediated killing.

show abstract

In susceptible mice, Leishmania major induce very rapid interleukin‐4 production by CD4⁺ T cells which are NK1.1⁻

Cited by 155 publications

References 62 publications

Dissociation of disease susceptibility, inflammation and cytokine profile in lmr1/2 congenic mice infected with Leishmania major

Dissociation of disease susceptibility, inflammation and cytokine profile in lmr1/2 congenic mice infected with Leishmania major

In BALB/c Mice, IL-4 Production During the Initial Phase of Infection withLeishmania majorIs Necessary and Sufficient to Instruct Th2 Cell Development Resulting in Progressive Disease

The Relative Contribution of IL-4 Receptor Signaling and IL-10 to Susceptibility toLeishmania major

Contact Info

Product

Resources

About