Impaired calcineurin signaling in myeloid cells results in downregulation of pentraxin-3 and increased susceptibility to aspergillosis

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F17%3A00065290" target="_blank" >RIV/00159816:_____/17:00065290 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1038/mi.2016.52" target="_blank" >http://dx.doi.org/10.1038/mi.2016.52</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/mi.2016.52" target="_blank" >10.1038/mi.2016.52</a>

Result language

angličtina

Original language name

Impaired calcineurin signaling in myeloid cells results in downregulation of pentraxin-3 and increased susceptibility to aspergillosis

Original language description

Treatment of post-transplant patients with immunosuppressive drugs targeting the calcineurin-nuclear factor of activated T cells (NFAT) pathway, including cyclosporine A or tacrolimus, is commonly associated with a higher incidence of opportunistic infections, such as Aspergillus fumigatus, which can lead to severe life-threatening conditions. A component of the A. fumigatus cell wall, β-glucan, is recognized by dendritic cells (DCs) via the Dectin-1 receptor, triggering downstream signaling that leads to calcineurin-NFAT binding, NFAT translocation, and transcription of NFAT-regulated genes. Here, we address the question of whether calcineurin signaling in CD11c-expressing cells, such as DCs, has a specific role in the innate control of A. fumigatus. Impairment of calcineurin in CD11c-expressing cells (CD11ccrecnb1loxP) significantly increased susceptibility to systemic A. fumigatus infection and to intranasal infection in irradiated mice undergoing bone marrow transplant. Global expression profiling of bone marrow-derived DCs identified calcineurin-regulated processes in the immune response to infection, including expression of pentraxin-3, an important antifungal defense protein. These results suggest that calcineurin inhibition directly impairs important immunoprotective functions of myeloid cells, as shown by the higher susceptibility of CD11ccrecnbloxP mice in models of systemic and invasive pulmonary aspergillosis, including after allogeneic bone marrow transplantation. These findings are relevant to the clinical management of transplant patients with severe Aspergillus infections

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30102 - Immunology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Mucosal Immunology

ISSN

1933-0219

e-ISSN

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Volume of the periodical

10

Issue of the periodical within the volume

2

Country of publishing house

US - UNITED STATES

Number of pages

11

Pages from-to

470-480

UT code for WoS article

000395810000018

EID of the result in the Scopus database

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