| First Author | Jones DE | Year | 2000 |
| Journal | J Immunol | Volume | 165 |
| Issue | 1 | Pages | 364-72 |
| PubMed ID | 10861073 | Mgi Jnum | J:123771 |
| Mgi Id | MGI:3719519 | Doi | 10.4049/jimmunol.165.1.364 |
| Citation | Jones DE, et al. (2000) IL-4-independent inhibition of IL-12 responsiveness during Leishmania amazonensis infection. J Immunol 165(1):364-72 |
| abstractText | Leishmania amazonensis induces a nonhealing infection in C3H mice, whereas infection with Leishmania major is self-healing. We found that C3H mice infected with L. amazonensis exhibited decreased IL-12 production, which could account for the susceptibility to this organism. However, exogenous IL-12 administration failed to induce a healing immune response. The failure of L. amazonensis-infected C3H mice to respond to IL-12 was associated with a specific defect in IL-12 receptor beta2 (IL-12Rbeta2) mRNA expression by CD4+ T cells. Furthermore, decreased IL-12Rbeta2 mRNA expression correlated with a decrease in the IL-12-signaling capacity of the lymph node (LN) cells. IL-4 did not contribute to susceptibility or down-regulation of the IL-12Rbeta2 subunit, because IL-4-/- mice remained susceptible to L. amazonensis infection, even after IL-12 administration, and CD4+ cells from infected IL-4-/- mice also had reduced expression of IL-12Rbeta2 mRNA. These results demonstrate that regulation of the IL-12 receptor, independent of IL-4, is a point of control for the immune response to leishmaniasis. In contrast to experimental L. major infections, where host genetics control susceptibility, these studies demonstrate that the lack of IL-12 responsiveness may be dictated by the pathogen, rather than the host. |
