Differential Regulation of IL-9-Expression after Infection with Leishmania major in Susceptible and Resistant Mice

Gessner, André; Blum, Horst; Röllinghoff, Martin

doi:10.1016/s0171-2985(11)80414-6

Cited by 147 publications

(120 citation statements)

References 31 publications

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“…During L. major infection in the mouse, no functionally active IL9 is detected in sera of either susceptible BALB/c or resistant C57BL/6 mice, but IL9 mRNA is expressed at higher levels in BALB/c lymph nodes and spleens and IL-9 protein produced at higher level after restimulation of lymphocytes in vitro. 9 In mice, the region on murine chromosome 11 that has conserved synteny with human chromosome 5q23.3-q33 has been specifically shown to be involved in controlling later phases of cutaneous lesion development and visceralisation of L. major in susceptible BALB/c mice. 10 Extensive visceralisation and death following L. major infection in susceptible BALB/c mice make it a better model of clinical visceral leishmaniasis than L. donovani infection in the mouse.…”

Section: Discussionmentioning

confidence: 99%

Genetic susceptibility to visceral leishmaniasis in The Sudan: linkage and association with IL4 and IFNGR1

et al. 2003

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Longitudinal studies in Sudan show ethnic differences in incidence and clinical phenotypes associated with Leishmania donovani. Immunologically, bias in type 1 vs type 2 cytokine responses is important. To determine whether polymorphisms at IL4/IL9 or IFNGR1 contribute to susceptibility, we examined 59 multicase families of visceral leishmaniasis (VL) with/without post Kala-azar dermal leishmaniasis (PKDL). Multipoint nonparametric analysis (Allegro) linked IL4/IL9 to VL per se (P ¼ 0.002). Transmission disequilibrium testing with robust variance estimates confirmed association in the presence of linkage between VL per se and IL4 (P ¼ 0.008) but not IL9. Stepwise logistic regression analysis showed both IL4RP2 and IL4RP1 markers contributed significantly to the association, suggesting a common disease-associated haplotype. In contrast, IFNGR1 was linked (P ¼ 0.031) and associated (P ¼ 0.007) to PKDL but not VL or VL per se. Hence, polymorphism in a type 2 cytokine gene influences underlying susceptibility to VL, whereas IFNGR1 is specifically related to susceptibility to PKDL.

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Section: Discussionmentioning

confidence: 99%

Genetic susceptibility to visceral leishmaniasis in The Sudan: linkage and association with IL4 and IFNGR1

et al. 2003

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“…24 and 25). Because of its restricted production by Th2 clones in vitro (27) and its expression in Th2-type responses in vivo (29 -31), IL-9 is considered to be a Th2 cytokine that can be induced via IL-4-dependent (26,27) and IL-4-independent (28) pathways. IL-10 dependence of IL-9 production has also been described in different models (28,39).…”

Section: Discussionmentioning

confidence: 99%

“…In vitro, IL-9 production by Th clones is restricted to the Th2 subset. Evidence indicates that IL-9 is also expressed in vivo during the course of Th2 responses, through the activation of IL-4-dependent (26,27) and IL-4-independent (28) mechanisms. While IL-9 has been shown to enhance resistance to helminths (29 -31), its potential role in acute Gram-negative infection has not been explored yet.…”

Section: Il-9 Protects Mice From Gram-negative Bacterial Shock: Supprmentioning

confidence: 99%

IL-9 Protects Mice from Gram-Negative Bacterial Shock: Suppression of TNF-α, IL-12, and IFN-γ, and Induction of IL-10

Grohmann

Snick

Campanile

et al. 2000

The Journal of Immunology

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IL-9 is a T cell-derived cytokine that, similar to the Th2 cytokines IL-4 and IL-10, has been implicated in the response to parasitic infections, allergy, and inflammatory processes. Because both IL-4 and IL-10 can confer protection to mice from septic shock, we investigated whether IL-9 may also be capable of conferring resistance on recipients of an otherwise lethal challenge with Pseudomonas aeruginosa. Prophylactic injections of rIL-9 appeared to be most effective in preventing the onset of a lethal shock, according to a pattern that was both dose dependent and time dependent. The protective effect of IL-9 was correlated with marked decreases in the production of the inflammatory mediators TNF-α, IL-12, and IFN-γ, as well as the induction of the anti-inflammatory cytokine IL-10. Sustained levels of IL-9-specific transcripts could be detected in the spleens of mice recovering from sublethal P. aeruginosa infection. Therefore, IL-9 may be protective in septic shock via a rather unique mechanism involving a complex modulation of inflammatory and anti-inflammatory mediators.

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“…37 The cDNA was synthesized in a 40 L reaction volume containing 50 mmol/L Tris HCl, pH 8.3, 2.5 mmol/L MgCl 2 , 10 mmol/L dNTP, 1 U Taq polymerase (Pharmacia Biotech), and 100 nmol/L primers during 35 cycles (1 minute denaturation at 94°C, 1 minute annealing at 58°C to 63°C, and 1 minute extension at 72°C). For amplification of ␥c, primers used were ␥c-sense primer 5Ј-CCCAGAGAAAGAAGAGCAAGCACC-3Ј and ␥c-antisense primer 5Ј-AAGGATTGATGTTCAGGCTTCCGG-3Ј.…”

Section: Rna Isolation Reverse Transcription and Polymerase Chain Rmentioning

confidence: 99%

A soluble form of the murine common γ chain is present at high concentrations in vivo and suppresses cytokine signaling

Meißner

Blum

Schnare

et al. 2001

Blood

Self Cite

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The common gamma-chain (␥c) is a component of the receptors for IL-2, IL-4, IL-7, IL-9, and IL-15 and is essential for their signal transduction. Western blotting and a newly established enzyme-linked immunosorbent assay detected substantial constitutive levels (50-250 ng/mL) of soluble ␥c (s␥c) in sera of murine inbred strains. It was demonstrated that purified immune cells, such as T, B, and natural killer cells, and macrophages released this protein after activation. Transfection experiments with cDNA encoding the fulllength ␥c showed that shedding of the transmembrane receptor led to the release of s␥c. The shedding enzymes, however, appeared to be distinct from those cleaving other cytokine receptors because inhibitors of metalloproteases (eg, TAPI) did not influence s␥c release. In vivo, superantigen-induced stimulation of T cells enhanced s␥c serum concentrations up to 10-fold within 6 hours. Because these findings demonstrated regulated expression of a yet unknown molecule in the immune response, further experiments were performed to assess the possible function(s) of s␥c. A physiological role of s␥c was indicated by its capacity to specifically inhibit cell growth induced by ␥c-dependent cytokines. Mutational analysis revealed that the Cterminus and the WSKWS motif are essential for the cytokine inhibitory effect of the s␥c and for binding of the molecule to cytokine receptor-expressing cells. Thus, competitive displacement of the transmembrane ␥c by excess s␥c is the most likely mechanism of cell growth inhibition. It was implied that naturally produced s␥c is a negative modulator of ␥c-dependent cytokines. IntroductionThe murine common gamma-chain (␥c) is a 64-kd type 1 transmembrane protein of the cytokine receptor family. 1 Although the ␥c alone is unable to bind to cytokines, it has been shown to be an essential component of the cell surface receptor complexes of IL-2, IL-4, IL-7, IL-9, and IL-15. 1 Interaction of the respective cytokines with the ␥c within the receptor complexes results in the activation of the Janus kinase JAK3, 2 which subsequently interacts with Pyk2, a member of focal adhesion tyrosine kinases, leading to the phosphorylation of this protein. 3 Recent studies have shown that the ␥c is critical for lymphoid development because genetic defects of either this molecule 4 or JAK3 5 in humans or targeted deletions of the ␥c 6,7 or JAK3 8-10 in mice severely impair the development of T and B cells, leading to severe combined immune deficiency syndromes (SCID). 11 Soluble cytokine receptors and growth factor receptors are present as immunomodulatory molecules in body fluids of humans and mice (reviewed in references 12 and 14). Two major nonexclusive mechanisms are responsible for the generation of soluble cytokine receptors: proteolytic cleavage of transmembrane receptors catalyzed mostly by metalloproteases [15][16][17][18][19] or de novo synthesis of alternatively spliced mRNAs encoding soluble receptor molecules lacking a transmembrane domain. [20][21][22][23][24][25][26][27][28] ...

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Differential Regulation of IL-9-Expression after Infection with Leishmania major in Susceptible and Resistant Mice

Cited by 147 publications

References 31 publications

Genetic susceptibility to visceral leishmaniasis in The Sudan: linkage and association with IL4 and IFNGR1

Genetic susceptibility to visceral leishmaniasis in The Sudan: linkage and association with IL4 and IFNGR1

IL-9 Protects Mice from Gram-Negative Bacterial Shock: Suppression of TNF-α, IL-12, and IFN-γ, and Induction of IL-10

A soluble form of the murine common γ chain is present at high concentrations in vivo and suppresses cytokine signaling

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