Work

Myeloid Differentiation Factor 88 and Interleukin-1R1 Signaling Contribute to Resistance to Coccidioides immitis

Year: 2018

Type: article

Abstract: ABSTRACT Rodents are a natural host for the dimorphic pathogenic fungi Coccidioides immitis and Coccidioides posadasii , and mice are a good model for human infection. Humans and rodents both express Dectin-1 and Toll-like receptor 2 (TLR2) on myeloid cells, and those receptors collaborate to maximize the cytokine/chemokine responses to spherules (the tissue form of the fungi) and to formalin-killed spherules (FKS). We showed that Dectin-1 is necessary for resistance to pulmonary coccidioidomycosis, but the importance of TLR2 in vivo is uncertain. Myeloid differentiation factor 88 (MyD88) is the adapter protein for TLR2 and -4, interleukin-1R1 (IL-1R1), and IL-18R1. MyD88/TRIF −/− and MyD88 −/− mice were equally susceptible to C. immitis infection, in contrast to C57BL/6 (B6) controls. Of the four surface receptors, only IL-1R1 was required for resistance to C. immitis , partially explaining the susceptibility of MyD88 −/− mice. We also found that FKS stimulated production of IL-1Ra by bone marrow-derived dendritic cells (BMDCs), independent of MyD88 and Dectin-1. There also was a very high concentration of IL-1Ra in the lungs of infected B6 mice, supporting the potential importance of this regulatory IL-1 family protein in the largely ineffective response of B6 mice to coccidioidomycosis. These results suggest that IL-1R1 signaling is important for defense against C. immitis infection.

Source: Infection and Immunity

DOI: 10.1128/iai.00028-18

Authors: Suganya Viriyakosol, Lorraine Walls, Sharon Okamoto, Eyal Raz, David L. Williams, Joshua Fierer

Institutions: UC San Diego Health System, University of California San Diego, VA San Diego Healthcare System, East Tennessee State University

Language: English

Topic: Fungal Infections and Studies

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases