• Something wrong with this record ?

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

T. Zelante, AY. Wong, A. Mencarelli, S. Foo, F. Zolezzi, B. Lee, M. Poidinger, P. Ricciardi-Castagnoli, J. Fric,

. 2017 ; 10 (2) : 470-480. [pub] 20160615

Language English Country United States

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc18017206

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.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc18017206
003      
CZ-PrNML
005      
20180524110316.0
007      
ta
008      
180515s2017 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1038/mi.2016.52 $2 doi
035    __
$a (PubMed)27301880
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Zelante, T $u Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore. Department of Experimental Medicine, University of Perugia, Perugia, Italy.
245    10
$a Impaired calcineurin signaling in myeloid cells results in downregulation of pentraxin-3 and increased susceptibility to aspergillosis / $c T. Zelante, AY. Wong, A. Mencarelli, S. Foo, F. Zolezzi, B. Lee, M. Poidinger, P. Ricciardi-Castagnoli, J. Fric,
520    9_
$a 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.
650    _2
$a zvířata $7 D000818
650    _2
$a aspergilóza $x imunologie $7 D001228
650    _2
$a Aspergillus fumigatus $x imunologie $7 D001232
650    12
$a transplantace kostní dřeně $7 D016026
650    _2
$a C-reaktivní protein $x genetika $x metabolismus $7 D002097
650    _2
$a antigeny CD11c $x metabolismus $7 D039521
650    _2
$a kalcineurin $x genetika $x metabolismus $7 D019703
650    _2
$a inhibitory kalcineurinu $x škodlivé účinky $x terapeutické užití $7 D065095
650    _2
$a kultivované buňky $7 D002478
650    _2
$a dendritické buňky $x imunologie $7 D003713
650    _2
$a náchylnost k nemoci $7 D004198
650    _2
$a down regulace $7 D015536
650    _2
$a rejekce štěpu $x prevence a kontrola $7 D006084
650    _2
$a lidé $7 D006801
650    _2
$a imunosupresiva $x škodlivé účinky $x terapeutické užití $7 D007166
650    _2
$a myši $7 D051379
650    _2
$a myši inbrední BALB C $7 D008807
650    _2
$a myši inbrední C57BL $7 D008810
650    _2
$a myši knockoutované $7 D018345
650    _2
$a sérový amyloidový protein $x genetika $x metabolismus $7 D000683
650    _2
$a signální transdukce $7 D015398
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Wong, A Y W $u Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore. National University of Singapore Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore.
700    1_
$a Mencarelli, A $u Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore. Emerging Infectious Diseases Programme, Duke-NUS, Singapore.
700    1_
$a Foo, S $u Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.
700    1_
$a Zolezzi, F $u Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.
700    1_
$a Lee, B $u Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.
700    1_
$a Poidinger, M $u Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore. Department of Biological Sciences, National University of Singapore, Singapore.
700    1_
$a Ricciardi-Castagnoli, P $u Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.
700    1_
$a Fric, J $u Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore. Center for Translational Medicine, International Clinical Research Center, St Anne's University Hospital Brno, Brno, Czech Republic.
773    0_
$w MED00195155 $t Mucosal immunology $x 1935-3456 $g Roč. 10, č. 2 (2017), s. 470-480
856    41
$u https://pubmed.ncbi.nlm.nih.gov/27301880 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20180515 $b ABA008
991    __
$a 20180524110502 $b ABA008
999    __
$a ok $b bmc $g 1300830 $s 1014046
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2017 $b 10 $c 2 $d 470-480 $e 20160615 $i 1935-3456 $m Mucosal immunology $n Mucosal Immunol $x MED00195155
LZP    __
$a Pubmed-20180515

Find record

Citation metrics

Archiving options