Disruption of CD40-CD40 ligand interactions results in an enhanced susceptibility to Leishmania amazonensis infection

Lynn Soong; Jian Chao Xu; Iqbal S. Grewal; Peter Kima; Jiaren Sun; B. Jack Longley; Nancy H. Ruddle; Diane McMahon-Pratt; Richard A. Flavell

doi:10.1016/S1074-7613(00)80434-3

Disruption of CD40-CD40 ligand interactions results in an enhanced susceptibility to Leishmania amazonensis infection

Lynn Soong, Jian Chao Xu, Iqbal S. Grewal, Peter Kima, Jiaren Sun, B. Jack Longley, Nancy H. Ruddle, Diane McMahon-Pratt, Richard A. Flavell

Research output: Contribution to journal › Article › peer-review

258 Scopus citations

Abstract

To study the role of CD40 ligand (CD40L) in the host immune responses against intracellular pathogens, we infected CD40L knockout (CD40L(-/-)) mice with Leishmania amazonensis. Although wild-type mice were susceptible to infection and developed progressive ulcerative lesions, tissue parasite burdens in CD40L(-/-) mice were significantly higher. This heightened susceptibility to infection was associated with an impaired T cell and macrophage activation and altered inflammatory response, as reflected by low levels of IFNγ, lymphotoxin-tumor necrosis factor (LT-TNF), and nitric oxide (NO) production. Furthermore, CD40L(-/-) mice failed to generate a protective immune response after immunization. These results indicate an essential role of cognate CD40-CD40L interactions in the generation of cellular immune responses against an intracellular parasite.

Original language	English (US)
Pages (from-to)	263-273
Number of pages	11
Journal	Immunity
Volume	4
Issue number	3
DOIs	https://doi.org/10.1016/S1074-7613(00)80434-3
State	Published - Mar 1996
Externally published	Yes

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Infectious Diseases

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10.1016/S1074-7613(00)80434-3

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@article{9f2559126c59401783e228fb0e4daacf,

title = "Disruption of CD40-CD40 ligand interactions results in an enhanced susceptibility to Leishmania amazonensis infection",

abstract = "To study the role of CD40 ligand (CD40L) in the host immune responses against intracellular pathogens, we infected CD40L knockout (CD40L(-/-)) mice with Leishmania amazonensis. Although wild-type mice were susceptible to infection and developed progressive ulcerative lesions, tissue parasite burdens in CD40L(-/-) mice were significantly higher. This heightened susceptibility to infection was associated with an impaired T cell and macrophage activation and altered inflammatory response, as reflected by low levels of IFNγ, lymphotoxin-tumor necrosis factor (LT-TNF), and nitric oxide (NO) production. Furthermore, CD40L(-/-) mice failed to generate a protective immune response after immunization. These results indicate an essential role of cognate CD40-CD40L interactions in the generation of cellular immune responses against an intracellular parasite.",

author = "Lynn Soong and Xu, {Jian Chao} and Grewal, {Iqbal S.} and Peter Kima and Jiaren Sun and {Jack Longley}, B. and Ruddle, {Nancy H.} and Diane McMahon-Pratt and Flavell, {Richard A.}",

note = "Funding Information: Correspondence should be addressed to D. M.-P. and R. A. F. We would like to thank C. Bergman for measuring LT–TNF activity, Drs. S. Constant and K. Bottomly for providing reagents for IgE ELISA and B7-2 staining, Drs. S. Reiner and R. Locksley for providing the pQRS plasmid, and Dr. F. Heinzel for providing anti-IL-12 antibodies. J.-C. X. and I. S. G. are associates, and R. A. F. is an investigator of the Howard Hughes Medical Institute. This work was supported in part by grants from the National Institutes of Health to D. M.-P. (AI27811 and AI23004).",

year = "1996",

month = mar,

doi = "10.1016/S1074-7613(00)80434-3",

language = "English (US)",

volume = "4",

pages = "263--273",

journal = "Immunity",

issn = "1074-7613",

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T1 - Disruption of CD40-CD40 ligand interactions results in an enhanced susceptibility to Leishmania amazonensis infection

AU - Soong, Lynn

AU - Xu, Jian Chao

AU - Grewal, Iqbal S.

AU - Kima, Peter

AU - Sun, Jiaren

AU - Jack Longley, B.

AU - Ruddle, Nancy H.

AU - McMahon-Pratt, Diane

AU - Flavell, Richard A.

N1 - Funding Information: Correspondence should be addressed to D. M.-P. and R. A. F. We would like to thank C. Bergman for measuring LT–TNF activity, Drs. S. Constant and K. Bottomly for providing reagents for IgE ELISA and B7-2 staining, Drs. S. Reiner and R. Locksley for providing the pQRS plasmid, and Dr. F. Heinzel for providing anti-IL-12 antibodies. J.-C. X. and I. S. G. are associates, and R. A. F. is an investigator of the Howard Hughes Medical Institute. This work was supported in part by grants from the National Institutes of Health to D. M.-P. (AI27811 and AI23004).

PY - 1996/3

Y1 - 1996/3

N2 - To study the role of CD40 ligand (CD40L) in the host immune responses against intracellular pathogens, we infected CD40L knockout (CD40L(-/-)) mice with Leishmania amazonensis. Although wild-type mice were susceptible to infection and developed progressive ulcerative lesions, tissue parasite burdens in CD40L(-/-) mice were significantly higher. This heightened susceptibility to infection was associated with an impaired T cell and macrophage activation and altered inflammatory response, as reflected by low levels of IFNγ, lymphotoxin-tumor necrosis factor (LT-TNF), and nitric oxide (NO) production. Furthermore, CD40L(-/-) mice failed to generate a protective immune response after immunization. These results indicate an essential role of cognate CD40-CD40L interactions in the generation of cellular immune responses against an intracellular parasite.

AB - To study the role of CD40 ligand (CD40L) in the host immune responses against intracellular pathogens, we infected CD40L knockout (CD40L(-/-)) mice with Leishmania amazonensis. Although wild-type mice were susceptible to infection and developed progressive ulcerative lesions, tissue parasite burdens in CD40L(-/-) mice were significantly higher. This heightened susceptibility to infection was associated with an impaired T cell and macrophage activation and altered inflammatory response, as reflected by low levels of IFNγ, lymphotoxin-tumor necrosis factor (LT-TNF), and nitric oxide (NO) production. Furthermore, CD40L(-/-) mice failed to generate a protective immune response after immunization. These results indicate an essential role of cognate CD40-CD40L interactions in the generation of cellular immune responses against an intracellular parasite.

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Disruption of CD40-CD40 ligand interactions results in an enhanced susceptibility to Leishmania amazonensis infection

Abstract

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