| First Author | Kautz-Neu K | Year | 2011 |
| Journal | J Invest Dermatol | Volume | 131 |
| Issue | 8 | Pages | 1650-9 |
| PubMed ID | 21525884 | Mgi Jnum | J:182062 |
| Mgi Id | MGI:5314674 | Doi | 10.1038/jid.2011.99 |
| Citation | Kautz-Neu K, et al. (2011) A role for leukocyte-derived IL-1RA in DC homeostasis revealed by increased susceptibility of IL-1RA-deficient mice to cutaneous leishmaniasis. J Invest Dermatol 131(8):1650-9 |
| abstractText | Dendritic cell (DC)-derived IL-1alpha/beta plays a critical role in the induction of T helper type 1 (Th1)-dependent immunity against Leishmania. DCs from susceptible BALB/c mice produce less IL-1alpha/beta when compared with resistant C57BL/6 mice, contributing to aberrant Th2 development and ultimate death of infected mice. We have extended our studies of the role of IL-1 in leishmaniasis using IL-1RA(-/-) BALB/c mice that are characterized by upregulated IL-1 receptor signaling. Unexpectedly, infection of IL-1RA(-/-) mice led to significantly worsened disease outcome with larger lesions, dramatically higher parasite burdens, and decreased IFN-gamma production by antigen-specific T cells. We determined that IL-1RA(-/-) DCs were more mature already in the steady state, exhibited less phagocytotic capacity, and IL-12 production in response to various stimuli was impaired. Our data suggest that in addition to effects on Th education, IL-1alpha/beta signaling also modulates DC homeostasis with increased signaling, leading to downmodulation of IL-12 synthesis and worsened disease outcome after infection with Leishmania major. Thus, the complex regulation of various members of the IL-1 cytokine family mediated through effects on both DCs and T cells critically contributes to disease outcome against this important human pathogen. |
