| First Author | Gundra UM | Year | 2011 |
| Journal | Infect Immun | Volume | 79 |
| Issue | 7 | Pages | 2586-96 |
| PubMed ID | 21482681 | Mgi Jnum | J:173498 |
| Mgi Id | MGI:5014152 | Doi | 10.1128/IAI.00920-10 |
| Citation | Gundra UM, et al. (2011) Increased Disease Severity of Parasite-Infected TLR2-/- 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. Infect Immun 79(7):2586-96 |
| abstractText | In a murine model for neurocysticercosis (NCC), intracranial inoculation of the helminth parasite Mesocestoides corti induces multiple Toll-like receptors (TLRs), among which TLR2 is upregulated first and to a relatively high extent. Here, we report that TLR2(-/-) 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(-/-) 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(+) myeloid cells, gammadelta T cells, alphabeta T cells, and B cells in the brains of parasite-infected TLR2(-/-) mice. This correlated with significantly reduced levels of inflammatory mediators, including tumor necrosis factor alpha (TNF-alpha), gamma interferon (IFN-gamma), CCL2, CCL3, and interleukin-6 (IL-6) in the central nervous system (CNS) of TLR2(-/-) 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(-/-) mice was compared with that in WT mice. Parasite-infected WT brains showed larger numbers of macrophages/microglia (CD11b(+) cells) expressing AAM-associated molecules such as YM1, Fizz1 (found in inflammatory zone-1 antigen), and arginase 1 than TLR2(-/-) 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. |
