{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:23:41Z","timestamp":1791318221726,"version":"4.3.1"},"reference-count":50,"publisher":"Rockefeller University Press","issue":"7","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1999,4,5]]},"abstract":"<jats:p>Although interferon (IFN)-\u03b3\u2013activated, mononuclear phagocytes are considered to be the major effectors of resistance to intracellular pathogens, it is unclear how they control the growth of microorganisms that reside in nonhemopoietic cells. Pathogens within such cells may be killed by metabolites secreted by activated macrophages or, alternatively, directly controlled by cytokine-induced microbicidal mechanisms triggered within infected nonphagocytic cells. To distinguish between these two basic mechanisms of cell-mediated immunity, reciprocal bone marrow chimeras were constructed between wild-type and IFN-\u03b3 receptor\u2013deficient mice and their survival assessed following infection with Toxoplasma gondii, a protozoan parasite that invades both hemopoietic and nonhemopoietic cell lineages. Resistance to acute and persistent infection was displayed only by animals in which IFN-\u03b3 receptors were expressed in both cellular compartments. Parallel chimera experiments performed with tumor necrosis factor (TNF) receptor\u2013deficient mice also indicated a codependence on hemopoietic and nonhemopoietic lineages for optimal control of the parasite. In contrast, in mice chimeric for inducible nitric oxide synthase (iNOS), an enzyme associated with IFN-\u03b3\u2013induced macrophage microbicidal activity, expression by cells of hemopoietic origin was sufficient for host resistance. Together, these findings suggest that, in concert with bone marrow\u2013derived effectors, nonhemopoietic cells can directly mediate, in the absence of endogenous iNOS, IFN-\u03b3\u2013 and TNF-\u03b1\u2013dependent host resistance to intracellular infection.<\/jats:p>","DOI":"10.1084\/jem.189.7.1083","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:33Z","timestamp":1027702113000},"page":"1083-1092","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":213,"title":["Effector Cells of Both Nonhemopoietic and Hemopoietic Origin Are Required for Interferon (IFN)-\u03b3\u2013 and Tumor Necrosis Factor (TNF)-\u03b1\u2013dependent Host Resistance to the Intracellular Pathogen, <i>Toxoplasma gondii <\/i>"],"prefix":"10.1084","volume":"189","author":[{"given":"George S.","family":"Yap","sequence":"first","affiliation":[{"name":"From the Immunobiology Section, Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Sher","sequence":"additional","affiliation":[{"name":"From the Immunobiology Section, Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1999,4,5]]},"reference":[{"key":"2023072508430249400_B1","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/0952-7915(95)80093-X","article-title":"Effects of IL-12 on immune responses to microbial infection: a key mediator in regulating disease outcome","volume":"7","author":"Biron","year":"1995","journal-title":"Curr Opin Immunol"},{"key":"2023072508430249400_B2","first-page":"1021","article-title":"Expression pattern and cellular origin of cytokines in normal and Toxoplasma gondiiinfected brain","volume":"150","author":"Schluter","year":"1997","journal-title":"Am J Pathol"},{"key":"2023072508430249400_B3","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1084\/jem.174.4.755","article-title":"Antileishmanial defense in macrophages triggered by tumor necrosis factor expressed on CD4+T lymphocyte plasma membrane","volume":"174","author":"Sypek","year":"1991","journal-title":"J Exp Med"},{"key":"2023072508430249400_B4","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/j.1600-065X.1997.tb00987.x","article-title":"Why listeriosis? 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