{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:34:29Z","timestamp":1781105669899,"version":"3.54.1"},"reference-count":28,"publisher":"National Academy of Sciences","issue":"51","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,12,21]]},"abstract":"<jats:p>\n                    Millions of people harbor latent infections of the fungus\n                    <jats:italic>Histoplasma capsulatum<\/jats:italic>\n                    . Such persistent infections represent a stalemate between mechanisms of virulence and the immune response. The differing responses of inbred mouse strains to the same pathogen reflect variation in the genes that control the outcome of infection. Here we show that a 250-fold difference in\n                    <jats:italic>H. capsulatum<\/jats:italic>\n                    susceptibility between inbred mouse strains is attributable to the genotype at the MHC\n                    <jats:italic>H2<\/jats:italic>\n                    locus. Gene expression analysis of strains varying only at the\n                    <jats:italic>H2<\/jats:italic>\n                    locus identified genotype-specific and genotype-independent expression signatures, including infection-induced genes such as the fungal pattern recognition receptor\n                    <jats:italic>Clec7a<\/jats:italic>\n                    . Surprisingly, B-cell\u2013specific gene expression was negatively correlated with fungal burden, whereas neutrophil-specific genes were correlated with superior disease outcome. Indeed, disease outcome improved when B cells were eliminated and neutrophils were more active, a previously unknown aspect of the host response. These data refine the understanding of genetic influences on histoplasmosis, reveal how shifts in the composition of immune cell populations compel different disease outcomes, and uncover how innate immunity modulation alters histoplasmosis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1012925108","type":"journal-article","created":{"date-parts":[[2010,12,6]],"date-time":"2010-12-06T23:17:29Z","timestamp":1291677449000},"page":"22202-22206","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":2,"title":["Genetic control of immune cell types in fungal disease"],"prefix":"10.1073","volume":"107","author":[{"given":"Jacob A.","family":"Mayfield","sequence":"first","affiliation":[{"name":"California Institute for Quantitative Biosciences and"},{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3220."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary F.","family":"Fontana","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3220."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasper","family":"Rine","sequence":"additional","affiliation":[{"name":"California Institute for Quantitative Biosciences and"},{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3220."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,12,6]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2008.12.024"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5520(02)00039-9"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gene.6364411"},{"key":"e_1_3_3_4_2","first-page":"233","article-title":"Resistance mechanisms in murine experimental histoplasmosis","volume":"24","author":"Wu-Hsieh BA","year":"1993","unstructured":"BA Wu-Hsieh, Resistance mechanisms in murine experimental histoplasmosis. Arch Med Res 24, 233\u2013238 (1993).","journal-title":"Arch Med Res"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1286-4579(00)01253-3"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1080\/1369378031000137279"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.4.1473-1481.1998"},{"key":"e_1_3_3_8_2","first-page":"843","article-title":"Histocompatibility genes of the mouse, II: Production and analysis of isogenic resistant lines","volume":"21","author":"Snell GD","year":"1958","unstructured":"GD Snell, RB Jackson, Histocompatibility genes of the mouse, II: Production and analysis of isogenic resistant lines. J Natl Cancer Inst 21, 843\u2013877 (1958).","journal-title":"J Natl Cancer Inst"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gene.6364254"},{"key":"e_1_3_3_10_2","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.4049\/jimmunol.144.5.1957","article-title":"Characterization of the molecular defects in the mouse E beta f and E beta q genes: Implications for the origin of MHC polymorphism","volume":"144","author":"Begovich AB","year":"1990","unstructured":"AB Begovich, TH Vu, PP Jones, Characterization of the molecular defects in the mouse E beta f and E beta q genes: Implications for the origin of MHC polymorphism. J Immunol 144, 1957\u20131964 (1990).","journal-title":"J Immunol"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901316"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.11.7729"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1408"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.11.7404"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/gene.2008.23"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0609848104"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1109717"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(01)00481-X"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.10.5668-5672.2000"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80173-9"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfn253"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.3.1763"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.7.3681"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902011"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000360"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.2202\/1544-6115.1027"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0306-9877(95)90228-7"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1012925108","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T07:30:41Z","timestamp":1685863841000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1012925108"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,12,6]]},"references-count":28,"journal-issue":{"issue":"51","published-print":{"date-parts":[[2010,12,21]]}},"alternative-id":["10.1073\/pnas.1012925108"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1012925108","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,12,6]]},"assertion":[{"value":"2010-12-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}