Ity influences the production of IFN-γ by murine splenocytes stimulated in vitro with Salmonella typhimurium

Lakshmi Ramarathinam, David Niesel, Gary R. Klimpel

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The Ity-Lsh-Bcg genetic locus in the mouse has been documented to confer innate resistance to at least three intracellular pathogens: Salmonella typhimurium, Leishmania donovani, and Mycobacterium. Expression of the resistance gene(s) results in a slower net growth of these pathogens in the reticuloendothelial system early postinfection. Although it is clear that the resident macrophages in resistant mice are functionally superior with regard to antimicrobial activity, the exact mechanism(s) underlying the control exerted by this gene is not understood. Using S. typhimurium infection as a model, we have examined the influence of this resistance gene(s) on the production of IFN-γ, a cytokine known to play an important role in host-defense against several intracellular pathogens. We compared IFN-γ production by splenocytes from resistant (Ityr) and sensitive (Itys) inbred mouse strains after stimulation in vitro with S. typhimurium. Spleen cells from Ityr mouse strains produced significantly higher levels of IFN-γ when compared to spleen cells obtained from Itys mouse strains. Enhanced IFN-γ production was not a generalized response to bacteria. Listeria monocytogenes induced comparable levels of IFN-γ production from both Ityr (CBA/J) and Itys (C57BL/6) mice. Splenocytes from Ity congenic mouse strains displayed similar differences in the level of IFN-γ produced after S. typhimurium stimulation, with spleen cells from the Ityr strain producing significantly higher levels of IFN-γ when compared to spleen cells from the Itys strain. A requirement for adherent cells and/or adherent cell-derived factors has been documented for IFN-γ production by S. typhimurium-stimulated splenocytes. Interestingly, supernatant from adherent cells obtained from Ityr mouse strains was found to induce the production of significantly higher levels of IFN-γ when compared to adherent cell supernatant from Itys strains. Nylon wool nonadherent cells from Itys mouse strains produced high levels of IFN-γ when exposed to supernatants obtained from adherent cells of Ityr mouse strains. In contrast, nylon wool nonadherent cells from Ityr mouse strains produced reduced levels of IFN-γ when exposed to supernatant obtained from adherent cells of Itys mouse strains. Thus, modulation of IFN-γ production appears to be a function of the Ityr gene(s). This study documents for the first time that the Ity locus may play a role in controlling resistance to Salmonella infection by regulating IFN-γ production by NK cells.

Original languageEnglish (US)
Pages (from-to)3965-3972
Number of pages8
JournalJournal of Immunology
Volume150
Issue number9
StatePublished - May 1 1993

Fingerprint

Salmonella typhimurium
Spleen
Salmonella Infections
Wool
Nylons
In Vitro Techniques
Genes
Congenic Mice
Leishmania donovani
Mononuclear Phagocyte System
Inbred Strains Mice
Genetic Loci
Listeria monocytogenes
Mycobacterium
Inbred C57BL Mouse
Natural Killer Cells
Macrophages
Cytokines
Bacteria
Gene Expression

ASJC Scopus subject areas

  • Immunology

Cite this

Ity influences the production of IFN-γ by murine splenocytes stimulated in vitro with Salmonella typhimurium. / Ramarathinam, Lakshmi; Niesel, David; Klimpel, Gary R.

In: Journal of Immunology, Vol. 150, No. 9, 01.05.1993, p. 3965-3972.

Research output: Contribution to journalArticle

@article{9f1bcac131ad4a0a988e94c2a3a8c5d5,
title = "Ity influences the production of IFN-γ by murine splenocytes stimulated in vitro with Salmonella typhimurium",
abstract = "The Ity-Lsh-Bcg genetic locus in the mouse has been documented to confer innate resistance to at least three intracellular pathogens: Salmonella typhimurium, Leishmania donovani, and Mycobacterium. Expression of the resistance gene(s) results in a slower net growth of these pathogens in the reticuloendothelial system early postinfection. Although it is clear that the resident macrophages in resistant mice are functionally superior with regard to antimicrobial activity, the exact mechanism(s) underlying the control exerted by this gene is not understood. Using S. typhimurium infection as a model, we have examined the influence of this resistance gene(s) on the production of IFN-γ, a cytokine known to play an important role in host-defense against several intracellular pathogens. We compared IFN-γ production by splenocytes from resistant (Ityr) and sensitive (Itys) inbred mouse strains after stimulation in vitro with S. typhimurium. Spleen cells from Ityr mouse strains produced significantly higher levels of IFN-γ when compared to spleen cells obtained from Itys mouse strains. Enhanced IFN-γ production was not a generalized response to bacteria. Listeria monocytogenes induced comparable levels of IFN-γ production from both Ityr (CBA/J) and Itys (C57BL/6) mice. Splenocytes from Ity congenic mouse strains displayed similar differences in the level of IFN-γ produced after S. typhimurium stimulation, with spleen cells from the Ityr strain producing significantly higher levels of IFN-γ when compared to spleen cells from the Itys strain. A requirement for adherent cells and/or adherent cell-derived factors has been documented for IFN-γ production by S. typhimurium-stimulated splenocytes. Interestingly, supernatant from adherent cells obtained from Ityr mouse strains was found to induce the production of significantly higher levels of IFN-γ when compared to adherent cell supernatant from Itys strains. Nylon wool nonadherent cells from Itys mouse strains produced high levels of IFN-γ when exposed to supernatants obtained from adherent cells of Ityr mouse strains. In contrast, nylon wool nonadherent cells from Ityr mouse strains produced reduced levels of IFN-γ when exposed to supernatant obtained from adherent cells of Itys mouse strains. Thus, modulation of IFN-γ production appears to be a function of the Ityr gene(s). This study documents for the first time that the Ity locus may play a role in controlling resistance to Salmonella infection by regulating IFN-γ production by NK cells.",
author = "Lakshmi Ramarathinam and David Niesel and Klimpel, {Gary R.}",
year = "1993",
month = "5",
day = "1",
language = "English (US)",
volume = "150",
pages = "3965--3972",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "9",

}

TY - JOUR

T1 - Ity influences the production of IFN-γ by murine splenocytes stimulated in vitro with Salmonella typhimurium

AU - Ramarathinam, Lakshmi

AU - Niesel, David

AU - Klimpel, Gary R.

PY - 1993/5/1

Y1 - 1993/5/1

N2 - The Ity-Lsh-Bcg genetic locus in the mouse has been documented to confer innate resistance to at least three intracellular pathogens: Salmonella typhimurium, Leishmania donovani, and Mycobacterium. Expression of the resistance gene(s) results in a slower net growth of these pathogens in the reticuloendothelial system early postinfection. Although it is clear that the resident macrophages in resistant mice are functionally superior with regard to antimicrobial activity, the exact mechanism(s) underlying the control exerted by this gene is not understood. Using S. typhimurium infection as a model, we have examined the influence of this resistance gene(s) on the production of IFN-γ, a cytokine known to play an important role in host-defense against several intracellular pathogens. We compared IFN-γ production by splenocytes from resistant (Ityr) and sensitive (Itys) inbred mouse strains after stimulation in vitro with S. typhimurium. Spleen cells from Ityr mouse strains produced significantly higher levels of IFN-γ when compared to spleen cells obtained from Itys mouse strains. Enhanced IFN-γ production was not a generalized response to bacteria. Listeria monocytogenes induced comparable levels of IFN-γ production from both Ityr (CBA/J) and Itys (C57BL/6) mice. Splenocytes from Ity congenic mouse strains displayed similar differences in the level of IFN-γ produced after S. typhimurium stimulation, with spleen cells from the Ityr strain producing significantly higher levels of IFN-γ when compared to spleen cells from the Itys strain. A requirement for adherent cells and/or adherent cell-derived factors has been documented for IFN-γ production by S. typhimurium-stimulated splenocytes. Interestingly, supernatant from adherent cells obtained from Ityr mouse strains was found to induce the production of significantly higher levels of IFN-γ when compared to adherent cell supernatant from Itys strains. Nylon wool nonadherent cells from Itys mouse strains produced high levels of IFN-γ when exposed to supernatants obtained from adherent cells of Ityr mouse strains. In contrast, nylon wool nonadherent cells from Ityr mouse strains produced reduced levels of IFN-γ when exposed to supernatant obtained from adherent cells of Itys mouse strains. Thus, modulation of IFN-γ production appears to be a function of the Ityr gene(s). This study documents for the first time that the Ity locus may play a role in controlling resistance to Salmonella infection by regulating IFN-γ production by NK cells.

AB - The Ity-Lsh-Bcg genetic locus in the mouse has been documented to confer innate resistance to at least three intracellular pathogens: Salmonella typhimurium, Leishmania donovani, and Mycobacterium. Expression of the resistance gene(s) results in a slower net growth of these pathogens in the reticuloendothelial system early postinfection. Although it is clear that the resident macrophages in resistant mice are functionally superior with regard to antimicrobial activity, the exact mechanism(s) underlying the control exerted by this gene is not understood. Using S. typhimurium infection as a model, we have examined the influence of this resistance gene(s) on the production of IFN-γ, a cytokine known to play an important role in host-defense against several intracellular pathogens. We compared IFN-γ production by splenocytes from resistant (Ityr) and sensitive (Itys) inbred mouse strains after stimulation in vitro with S. typhimurium. Spleen cells from Ityr mouse strains produced significantly higher levels of IFN-γ when compared to spleen cells obtained from Itys mouse strains. Enhanced IFN-γ production was not a generalized response to bacteria. Listeria monocytogenes induced comparable levels of IFN-γ production from both Ityr (CBA/J) and Itys (C57BL/6) mice. Splenocytes from Ity congenic mouse strains displayed similar differences in the level of IFN-γ produced after S. typhimurium stimulation, with spleen cells from the Ityr strain producing significantly higher levels of IFN-γ when compared to spleen cells from the Itys strain. A requirement for adherent cells and/or adherent cell-derived factors has been documented for IFN-γ production by S. typhimurium-stimulated splenocytes. Interestingly, supernatant from adherent cells obtained from Ityr mouse strains was found to induce the production of significantly higher levels of IFN-γ when compared to adherent cell supernatant from Itys strains. Nylon wool nonadherent cells from Itys mouse strains produced high levels of IFN-γ when exposed to supernatants obtained from adherent cells of Ityr mouse strains. In contrast, nylon wool nonadherent cells from Ityr mouse strains produced reduced levels of IFN-γ when exposed to supernatant obtained from adherent cells of Itys mouse strains. Thus, modulation of IFN-γ production appears to be a function of the Ityr gene(s). This study documents for the first time that the Ity locus may play a role in controlling resistance to Salmonella infection by regulating IFN-γ production by NK cells.

UR - http://www.scopus.com/inward/record.url?scp=0027287494&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027287494&partnerID=8YFLogxK

M3 - Article

C2 - 8473743

AN - SCOPUS:0027287494

VL - 150

SP - 3965

EP - 3972

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 9

ER -