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Here, we report that TLR2<jats:sup>\u2212\/\u2212<\/jats:sup>mice displayed significantly increased susceptibility to parasite infection accompanied by increased numbers of parasites in the brain parenchyma compared to infection in wild-type (WT) mice. This coincided with an increased display of microglial nodule formations and greater neuropathology than in the WT. Parasite-infected TLR2<jats:sup>\u2212\/\u2212<\/jats:sup>brains exhibited a scarcity of lymphocytic cuffing and displayed reduced numbers of infiltrating leukocytes. Fluorescence-activated cell sorter (FACS) analyses revealed significantly lower numbers of CD11b<jats:sup>+<\/jats:sup>myeloid cells, \u03b3\u03b4 T cells, \u03b1\u03b2 T cells, and B cells in the brains of parasite-infected TLR2<jats:sup>\u2212\/\u2212<\/jats:sup>mice. This correlated with significantly reduced levels of inflammatory mediators, including tumor necrosis factor alpha (TNF-\u03b1), gamma interferon (IFN-\u03b3), CCL2, CCL3, and interleukin-6 (IL-6) in the central nervous system (CNS) of TLR2<jats:sup>\u2212\/\u2212<\/jats:sup>mice. As TLR2 has been implicated in immune regulation of helminth infections and as alternatively activated macrophages (AAMs) are thought to play a profound regulatory role in such infections, induction of AAMs in infected TLR2<jats:sup>\u2212\/\u2212<\/jats:sup>mice was compared with that in WT mice. Parasite-infected WT brains showed larger numbers of macrophages\/microglia (CD11b<jats:sup>+<\/jats:sup>cells) expressing AAM-associated molecules such as YM1, Fizz1 (found in inflammatory zone-1 antigen), and arginase 1 than TLR2<jats:sup>\u2212\/\u2212<\/jats:sup>brains, consistent with a protective role of AAMs during infection. Importantly, these results demonstrate that TLR2-associated responses modulate the disease severity of murine NCC.<\/jats:p>","DOI":"10.1128\/iai.00920-10","type":"journal-article","created":{"date-parts":[[2011,4,12]],"date-time":"2011-04-12T05:29:37Z","timestamp":1302586177000},"page":"2586-2596","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":31,"title":["Increased Disease Severity of Parasite-Infected TLR2<sup>\u2212\/\u2212<\/sup>Mice Is Correlated with Decreased Central Nervous System Inflammation and Reduced Numbers of Cells with Alternatively Activated Macrophage Phenotypes in a Murine Model of Neurocysticercosis"],"prefix":"10.1128","volume":"79","author":[{"given":"Uma Mahesh","family":"Gundra","sequence":"first","affiliation":[{"name":"Department of Biology, South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, One UTSA Circle, San Antonio, Texas 78249-1644"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bibhuti B.","family":"Mishra","sequence":"additional","affiliation":[{"name":"Department of Biology, South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, One UTSA Circle, San Antonio, Texas 78249-1644"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kondi","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tampa General Hospital, One Tampa Circle, Tampa, Florida 33606"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judy M.","family":"Teale","sequence":"additional","affiliation":[{"name":"Department of Biology, South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, One UTSA Circle, San Antonio, Texas 78249-1644"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-006-0424-4"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000218"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2005.11.020"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2007.05.005"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2007.07.010"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1451"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2008.02826.x"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0083-6729(06)74009-2"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.3.1711"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.5.2634-2642.2003"},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"995","DOI":"10.4049\/jimmunol.162.2.995","article-title":"Development of an animal model for neurocysticercosis: immune response in the central nervous system is characterized by a predominance of \u03b3\u03b4 T cells","volume":"162","author":"Cardona A. 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