Non-ulcerative cutaneous lesion in immunodeficient mice with Leishmania amazonensis infection

Terabe, Masaki; Kuramochi, Takashi; Hatabu, Toshimitsu; Ito, Mamoru; Ueyama, Y; Katakura, Ken; Kawazu, Shin-ichiro; Onodera, Takashi; Matsumoto, Yoshitsugu

doi:10.1016/s1383-5769(98)00040-3

Cited by 17 publications

(15 citation statements)

References 18 publications

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“…As we reported previously (21), in ulcerated nodules of C.B-17 mice, the epidermis had been desquamated and the dermis was infiltrated with mononuclear and polymorphonuclear cells. The subcutaneous tissue was infiltrated with mononuclear and polymorphonuclear cells as well as vacuolated histiocytes which contained many amastigotes.…”

Section: Resultssupporting

confidence: 74%

CD4⁺Cells Are Indispensable for Ulcer Development in Murine Cutaneous Leishmaniasis

et al. 2000

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One of the most characteristic clinical features in cutaneous leishmaniasis is the development of nodules followed by ulcerations at the site of infection. Leishmania amazonensis-infected mice show similar ulcerative lesions. Leishmania-infected severe combined immunodeficiency (SCID) mice, however, have been shown to develop nonulcerative nodules. In the present study, the roles of T cells in ulceration were examined using SCID mice in cell reconstitution experiments. After development of nonulcerative nodules, SCID mice were inoculated with splenocytes from either Leishmania-infected or naive immunocompetent mice, resulting in ulceration in all mice. When naive splenocytes were depleted of CD4 ؉ , CD8 ؉ , or B220 ؉ cell populations and the remaining cells were injected into Leishmania-infected SCID mice after the development of nodules, only SCID mice inoculated with splenocytes depleted of CD4 ؉ cells did not show ulceration. The evidence obtained in this study clearly shows that the CD4 ؉ cell population is indispensable for ulceration in leishmaniasis lesions of SCID mice.

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Section: Resultssupporting

confidence: 74%

CD4⁺Cells Are Indispensable for Ulcer Development in Murine Cutaneous Leishmaniasis

et al. 2000

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“…However, circulating antibodies may also contribute to L. amazonensis pathogenesis (22) via multiple mechanisms, including antibody-mediated IL-10 production (19). We and others have previously shown that RAG2 Ϫ/Ϫ and major histocompatibility complex class II-negative mice are refractory to L. amazonensis infection, suggesting an essential role for CD4 ϩ T-cell-mediated responses in the immunopathogenesis of L. amazonensis infection (39,42).…”

mentioning

confidence: 99%

CXCL10/Gamma Interferon-Inducible Protein 10-Mediated Protection againstLeishmania amazonensisInfection in Mice

Vasquez¹,

Soong

2006

Infect Immun

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Leishmania amazonensis can cause progressive disease in most inbred strains of mice. We have previously shown that L. amazonensis-infected C57BL/6 mice have profound impairments in expression of proinflammatory cytokines and chemokines and in activation of antigen-specific CD4 ؉ T cells. These impairments are independent of interleukin-4 (IL-4) but partially due to IL-10 production. The precise mechanism of pathogenesis associated with L. amazonensis infection remains largely unresolved. Since chemokines are essential mediators of leukocyte recruitment and effector cell function, we hypothesized that these molecules are important for the initiation of early responses locally and for the eventual control of the infection. In this study, we examined the roles of CXCL10/gamma interferon-inducible protein 10 (IP-10) and CCL2/monocyte chemoattractant protein 1 (MCP-1) in the activation of the macrophage effector function in vitro and their efficacy in ameliorating infection in vivo. Bone marrow-derived macrophages of both BALB/c and C57BL/6 mice were treated with increasing concentrations of recombinant chemokines prior to infection with either stationaryphase promastigotes or tissue-derived amastigotes. We found that treatment with IP-10 or MCP-1 significantly reduced parasite burdens, in a dose-dependent manner, and triggered nitric oxide production. When susceptible C57BL/6 mice were injected locally with IP-10 following L. amazonensis infection, there was a significant delay in lesion development and a reduction in parasite burdens, accompanied by 7-and 3.5-fold increases in gamma interferon and IL-12 secretion, respectively, in restimulated lymph node cells. This study confirms that IP-10 plays a protective role in promoting the reduction of intracellular parasites and thereby opens new avenues for therapeutic control of nonhealing cutaneous leishmaniasis in the New World.

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“…Previous studies in our laboratory have demonstrated that CD4 + cells are indispensable for ulcer development in murine CL (20)(21)(22). In contrast, development of skin lesion associated with macrophage accumulation during murine CL does not require T cell or B cell (5,20,21).…”

Section: Ikhatanbaatar Sgantuya1 Dboldbaatar Others Journal Ofmentioning

confidence: 79%

“…For example, L. major infection causes the development of skin lesionin RAG2 -/-mice comparable to BALB/c mice, demonstrating T and B cell-independent mechanism for lesion development (5). In contrast, ulceration of the skin lesion in L. amazonensis infection is CD4 + T cell-dependent (20)(21)(22). Together, it is considered that the pathological mechanisms under various manifestations in leishmaniasis are not uniform, and understanding the mechanisms is important for the control of individual symptoms to develop new interventions.…”

Section: Discussionmentioning

confidence: 99%

Histopathological characterization of L. donovani infection in RAG2-/-mice

Khatanbaatar¹,

Gantuya²,

Boldbaatar³

et al. 2015

Mong. J. Agric. Sci.

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Non-ulcerative cutaneous lesion in immunodeficient mice with Leishmania amazonensis infection

Cited by 17 publications

References 18 publications

CD4⁺Cells Are Indispensable for Ulcer Development in Murine Cutaneous Leishmaniasis

CD4⁺Cells Are Indispensable for Ulcer Development in Murine Cutaneous Leishmaniasis

CXCL10/Gamma Interferon-Inducible Protein 10-Mediated Protection againstLeishmania amazonensisInfection in Mice

Histopathological characterization of L. donovani infection in RAG2-/-mice

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Non-ulcerative cutaneous lesion in immunodeficient mice with Leishmania amazonensis infection

Cited by 17 publications

References 18 publications

CD4+Cells Are Indispensable for Ulcer Development in Murine Cutaneous Leishmaniasis

CD4+Cells Are Indispensable for Ulcer Development in Murine Cutaneous Leishmaniasis

CXCL10/Gamma Interferon-Inducible Protein 10-Mediated Protection againstLeishmania amazonensisInfection in Mice

Histopathological characterization of L. donovani infection in RAG2-/-mice

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CD4⁺Cells Are Indispensable for Ulcer Development in Murine Cutaneous Leishmaniasis

CD4⁺Cells Are Indispensable for Ulcer Development in Murine Cutaneous Leishmaniasis