{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:18:46Z","timestamp":1790965126136,"version":"4.1.0"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"4","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,1,24]]},"abstract":"<jats:p>\n                    Obligate intracellular pathogens such as\n                    <jats:italic>Leishmania<\/jats:italic>\n                    specifically target host phagocytes for survival and replication. Phosphoinositide 3-kinase \u03b3 (PI3K\u03b3), a member of the class I PI3Ks that is highly expressed by leukocytes, controls cell migration by initiating actin polymerization and cytoskeletal reorganization, which are processes also critical for phagocytosis. In this study, we demonstrate that class IB PI3K, PI3K\u03b3, plays a critical role in pathogenesis of chronic cutaneous leishmaniasis caused by\n                    <jats:italic>L. mexicana<\/jats:italic>\n                    . Using the isoform-selective PI3K\u03b3 inhibitor, AS-605240 and PI3K\u03b3 gene-deficient mice, we show that selective blockade or deficiency of PI3K\u03b3 significantly enhances resistance against\n                    <jats:italic>L. mexicana<\/jats:italic>\n                    that is associated with a significant suppression of parasite entry into phagocytes and reduction in recruitment of host phagocytes as well as regulatory T cells to the site of infection. Furthermore, we demonstrate that AS-605240 is as effective as the standard antileishmanial drug sodium stibogluconate in treatment of cutaneous leishmaniasis caused by\n                    <jats:italic>L. mexicana<\/jats:italic>\n                    . These findings reveal a unique role for PI3K\u03b3 in\n                    <jats:italic>Leishmania<\/jats:italic>\n                    invasion and establishment of chronic infection, and demonstrate that therapeutic targeting of host pathways involved in establishment of infection may be a viable strategy for treating infections caused by obligate intracellular pathogens such as\n                    <jats:italic>Leishmania<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1073\/pnas.1110339109","type":"journal-article","created":{"date-parts":[[2012,1,9]],"date-time":"2012-01-09T20:43:26Z","timestamp":1326141806000},"page":"1251-1256","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":47,"title":["Critical role for phosphoinositide 3-kinase gamma in parasite invasion and disease progression of cutaneous leishmaniasis"],"prefix":"10.1073","volume":"109","author":[{"given":"Hannah E.","family":"Cummings","sequence":"first","affiliation":[{"name":"Department of Microbiology,"},{"name":"Department of Pathology, The Ohio State University Medical Center, Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Barbi","sequence":"additional","affiliation":[{"name":"Department of Microbiology,"},{"name":"Immunology and Hematopoiesis Division, The Johns Hopkins University School of Medicine, Baltimore, MD 21231;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Reville","sequence":"additional","affiliation":[{"name":"Department of Microbiology,"},{"name":"Department of Pathology, The Ohio State University Medical Center, Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Oghumu","sequence":"additional","affiliation":[{"name":"Department of Microbiology,"},{"name":"Department of Pathology, The Ohio State University Medical Center, Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Zorko","sequence":"additional","affiliation":[{"name":"Department of Microbiology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anasuya","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Davis Heart and Lung Research Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy L.","family":"Keiser","sequence":"additional","affiliation":[{"name":"Department of Microbiology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao","family":"Lu","sequence":"additional","affiliation":[{"name":"Ina Sue Perlmutter Laboratory, Children's Hospital, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"R\u00fcckle","sequence":"additional","affiliation":[{"name":"Merck Serono S.A., CH-1211 Geneva, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Varikuti","sequence":"additional","affiliation":[{"name":"Department of Microbiology,"},{"name":"Department of Pathology, The Ohio State University Medical Center, Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Lezama-Davila","sequence":"additional","affiliation":[{"name":"Department of Microbiology,"},{"name":"Department of Pathology, The Ohio State University Medical Center, Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark D.","family":"Wewers","sequence":"additional","affiliation":[{"name":"Davis Heart and Lung Research Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Whitacre","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danuta","family":"Radzioch","sequence":"additional","affiliation":[{"name":"Department of Medicine and Human Genetics, McGill University, Montreal, QC, Canada H3G 1A4;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Rommel","sequence":"additional","affiliation":[{"name":"Intellikine, Inc., San Diego, CA 92037; 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