A Role for Leukocyte-Derived IL-1RA in DC Homeostasis Revealed by Increased Susceptibility of IL-1RA-Deficient Mice to Cutaneous Leishmaniasis
| Autor: | Mark C. Udey, Esther von Stebut, Yoichiro Iwakura, Stephanie Dinges, Susanna Lopez Kostka, Kordula Kautz-Neu |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
medicine.medical_treatment
Leishmaniasis Cutaneous Bone Marrow Cells Dermatology Biochemistry Article Immunophenotyping Mice Phagocytosis Cutaneous leishmaniasis Downregulation and upregulation Immunity medicine Animals Leishmania major Molecular Biology Mice Inbred BALB C biology Leishmaniasis Dendritic Cells Dendritic cell Cell Biology Th1 Cells medicine.disease biology.organism_classification Leishmania Interleukin-12 Mice Mutant Strains Interleukin 1 Receptor Antagonist Protein Cytokine Immunology Disease Susceptibility Interleukin-1 |
| Zdroj: | Journal of Investigative Dermatology. 131(8):1650-1659 |
| ISSN: | 0022-202X |
| DOI: | 10.1038/jid.2011.99 |
| Popis: | Dendritic cell (DC)-derived IL-1α/β 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-1α/β 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-γ 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-1α/β 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|