An essential role for IL-13 in maintaining a non-healing response following Leishmania mexicana infection

Alexander, James; Brombacher, Frank; McGachy, H. Adrienne; McKenzie, Andrew N. J.; Walker, William B.; Carter, K. Christine

doi:10.1002/1521-4141(2002010)32:10<2923::aid-immu2923>3.0.co;2-e

Cited by 54 publications

(56 citation statements)

References 48 publications

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“…Similarly, substantial numbers of parasites were obtained from L. mexicana-infected BALB/c IL-4 Ϫ/Ϫ mice (15). Further, BALB/c IL-4 Ϫ/Ϫ mice, when also deficient in IL-13 gene, were found to express a significant amount of IL-10 during the infection, although the level was reduced in IL-4 Ϫ/Ϫ /IL-13 Ϫ/Ϫ mice compared with wild-type BALB/c mice (15). Based on our observations on IL-4 mRNA levels in IL-10 Ϫ/Ϫ mice, we predicted that in the absence of IL-10, treatment with anti-IL-4 mAb might promote effective resolution of infection.…”

Section: Course Of L Mexicana Infection In Anti-il-4-treated Il-10 ϫmentioning

confidence: 61%

“…The ability of IL-4R␣-deficient, but not IL-4-deficient, BALB/c mice to totally control the infection may be attributable to IL-13 in part compensating for IL-4 in IL-4-deficient mice (15). Interestingly with regard to the current study, the disease enhancing activity of IL-13 may be through its ability to up-regulate IL-10 production (30 -32) since mRNA transcripts for IL-10 are significantly suppressed L. mexicana infection in IL-13-deficient B6/129 mice (15). Confirmation that the IL-4 production in IL-10-deficient mice plays a significant role in the inability of these mice to control infection comes from our observation that lesions resolved in IL-10-deficient mice treated with anti-IL-4 mAb and that healed mice had few parasites in their lesions compared with nontreated IL-10-deficient mice or wild-type BALB/c mice treated with anti-IL-4 Ab.…”

Section: Discussionmentioning

confidence: 96%

“…This observation is similar to that in a recent study showing unimpaired IL-4 production by cells from L. mexicana-infected BALB/c mice lacking IL-4R␣ compared with infected wild-type mice, despite the fact that the IL-4R-deficient mice controlled infection and their cells produced increased amounts of IFN-␥ (15). The ability of IL-4R␣-deficient, but not IL-4-deficient, BALB/c mice to totally control the infection may be attributable to IL-13 in part compensating for IL-4 in IL-4-deficient mice (15). Interestingly with regard to the current study, the disease enhancing activity of IL-13 may be through its ability to up-regulate IL-10 production (30 -32) since mRNA transcripts for IL-10 are significantly suppressed L. mexicana infection in IL-13-deficient B6/129 mice (15).…”

Section: Discussionmentioning

confidence: 99%

“…However, despite the small lesion size and substantial reduction in parasite numbers, significant numbers of parasites (Ͼ10 5 footpad) were recovered from anti-IL-4-treated BALB/c mice suggesting the existence of additional factors mediating susceptibility to L. amazonensis infection (8). Similarly, substantial numbers of parasites were obtained from L. mexicana-infected BALB/c IL-4 Ϫ/Ϫ mice (15). Further, BALB/c IL-4 Ϫ/Ϫ mice, when also deficient in IL-13 gene, were found to express a significant amount of IL-10 during the infection, although the level was reduced in IL-4 Ϫ/Ϫ /IL-13 Ϫ/Ϫ mice compared with wild-type BALB/c mice (15).…”

Section: Course Of L Mexicana Infection In Anti-il-4-treated Il-10 ϫmentioning

confidence: 99%

“…Anti-IL-4 Ab treatment of BALB/c mice before infection with L. major or L. amazonensis reduces the parasite burden and controls the infection (8,14). Similarly IL-4 Ϫ/Ϫ mice on a BALB/c background have enhanced resistance to L. mexicana, as well as L. amazonensis infection (9,15).…”

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confidence: 99%

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The Role of Interleukin-10 in Susceptibility of BALB/c Mice to Infection with Leishmania mexicana and Leishmania amazonensis

Padigel

Alexander

Farrell

2003

The Journal of Immunology

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106

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Recent studies have demonstrated the critical role of IL-10 in susceptibility to cutaneous and visceral leishmaniasis caused by Leishmania major and Leishmania donovani, respectively. To determine whether IL-10 also plays a similar role in the susceptibility and pathogenesis of cutaneous leishmaniasis caused by the New World species, L. mexicana and L. amazonensis, we analyzed their course of infection in IL-10-deficient BALB/c mice and their wild-type counterparts. Although IL-10-deficient mice infected with either L. mexicana or L. amazonensis failed to control the lesion progression, we did observe consistently lower levels of infection in IL-10−/− mice compared with wild-type BALB/c mice. We also observed increased IFN-γ and NO production and higher levels for IL-12p40 and IL-12Rβ2 mRNA in cells from IL-10−/− mice compared with cells from BALB/c mice. The mRNA levels for IL-4, which increased significantly in both IL-10−/− and BALB/c mice, were comparable. When treated with anti-IL-4 mAb, IL-10−/− mice resolved the infection more effectively and had significantly fewer parasites in their lesions compared with similarly treated BALB/c mice. These findings suggest that IL-10, although not the dominant mediator of susceptibility of BALB/c mice to infection with L. mexicana and L. amazonensis, does play a significant role in regulating the development of a protective Th1-type response. However, effective resolution of infection with these New World parasites requires neutralization of both IL-4 and IL-10.

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Section: Course Of L Mexicana Infection In Anti-il-4-treated Il-10 ϫmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Course Of L Mexicana Infection In Anti-il-4-treated Il-10 ϫmentioning

confidence: 99%

mentioning

confidence: 99%

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The Role of Interleukin-10 in Susceptibility of BALB/c Mice to Infection with Leishmania mexicana and Leishmania amazonensis

Padigel

Alexander

Farrell

2003

The Journal of Immunology

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106

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Decreased IL‐10 and IL‐13 production and increased CD44^hi T cell recruitment contribute to Leishmania major immunity induced by non‐persistent parasites

et al. 2008

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Leishmaniasis is currently classified as category 1 disease, i.e. emerging and uncontrolled. Since the importance of persistent infection for maintaining an effective long‐lasting protective response is controversial, the present study asks whether immunisation with non‐persistent parasites leads to protection against Leishmania infection and to the recruitment of T cells of a specific phenotype. Our study shows that vaccination of susceptible BALB/c mice with live Leishmania major phosphomannomutase‐deficient parasites, which are avirulent and non‐persistent in vivo, leads to protection against infection. Immunisation with phosphomannomutase‐deficient parasites neither leads to differences in IFN‐γ, IL‐12, IL‐4 production nor alters the expression of effector and memory markers, including CD62L, IL‐7Rα and IL‐2Rα, when compared with unvaccinated controls. Observed protection is due to the ability of vaccinated animals to suppress early IL‐10 and IL‐13 production and to recruit a higher number of antigen‐experienced CD44hiCD4+ and CD44hiCD8+ T cells into draining LN following infection. Thus, expansion of T‐cell numbers and their rapid recruitment to LN upon infection as well as the restriction of IL‐13 and IL‐10 production leading to high IFN‐γ/IL‐10 ratio play an important role in protection against Leishmania affecting the outcome of the disease in favour of the host.

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Murine model of chronic L. (Viannia) panamensis infection: Role of IL‐13 in disease

et al. 2010

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Leishmania (Viannia) organisms are the most prevalent etiologic agents of human cutaneous leishmaniasis in the Americas. Nevertheless, our knowledge of the immunological mechanisms exploited by L. (Viannia) organisms remains limited and the mechanisms underlying disease are not well understood. Here, we report the development of a BALB/c mouse model of L. (V.) panamensis infection that is able to reproduce chronic disease, with persistent infection and clinically evident lesions for over 1 year. The immune response of the mouse resembles that found for L. (V.) panamensis-infected patients with chronic and recurrent lesions, presenting a mixed Th1/Th2 response with the presence of TNF-α, IFN-γ, IL-10 and IL-13. Using immunodeficient mice, the critical role for IL-13 and/or IL-4Rα in determining susceptibility to chronic infection was evident. With the induction of healing in the immunodeficient mice, increases in IFN-γ and IL-17 were found, concomitant with parasite control and elimination. Specifically, increases in CD4+ (but not CD8+) T cells producing IFN-γ were observed. These results suggest that IL-13 represents an important target for disease control of L. (V.) panamensis infection. This murine model should be useful to further understand the pathology associated with chronic disease and to develop methods for the treatment and prevention of leishmaniasis caused by L. (Viannia) parasites.

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An essential role for IL-13 in maintaining a non-healing response following Leishmania mexicana infection

Cited by 54 publications

References 48 publications

The Role of Interleukin-10 in Susceptibility of BALB/c Mice to Infection with Leishmania mexicana and Leishmania amazonensis

The Role of Interleukin-10 in Susceptibility of BALB/c Mice to Infection with Leishmania mexicana and Leishmania amazonensis

Decreased IL‐10 and IL‐13 production and increased CD44^hi T cell recruitment contribute to Leishmania major immunity induced by non‐persistent parasites

Murine model of chronic L. (Viannia) panamensis infection: Role of IL‐13 in disease

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An essential role for IL-13 in maintaining a non-healing response following Leishmania mexicana infection

Cited by 54 publications

References 48 publications

The Role of Interleukin-10 in Susceptibility of BALB/c Mice to Infection with Leishmania mexicana and Leishmania amazonensis

The Role of Interleukin-10 in Susceptibility of BALB/c Mice to Infection with Leishmania mexicana and Leishmania amazonensis

Decreased IL‐10 and IL‐13 production and increased CD44hi T cell recruitment contribute to Leishmania major immunity induced by non‐persistent parasites

Murine model of chronic L. (Viannia) panamensis infection: Role of IL‐13 in disease

Contact Info

Product

Resources

About

Decreased IL‐10 and IL‐13 production and increased CD44^hi T cell recruitment contribute to Leishmania major immunity induced by non‐persistent parasites