Toll-like receptor 4 and CD11b expressed on microglia coordinate eradication of Candida albicans cerebral mycosis

被引：14

作者：

Wu, Yifan ^{[1
,2
]}

Du, Shuqi ^{[3
]}

Bimler, Lynn H. ^{[1
]}

Mauk, Kelsey E. ^{[1
]}

Lortal, Lea ^{[4
]}

Kichik, Nessim ^{[4
]}

Griffiths, James S. ^{[4
]}

Osicka, Radim ^{[5
]}

Song, Lizhen ^{[1
]}

Polsky, Katherine ^{[1
]}

Kasper, Lydia ^{[6
]}

Sebo, Peter ^{[5
]}

Weatherhead, Jill ^{[1
,7
]}

Knight, J. Morgan ^{[8
]}

Kheradmand, Farrah ^{[1
,8
,9
,10
]}

Zheng, Hui ^{[3
,11
]}

Richardson, Jonathan P. ^{[4
]}

Hube, Bernhard ^{[6
,12
]}

Naglik, Julian R. ^{[4
]}

Corry, David B. ^{[1
,8
,9
,10
]}

机构：

[1] Baylor Coll Med, Dept Med, One Baylor Plaza, Houston, TX 77030 USA

[2] Baylor Coll Med, Dept Pediat, One Baylor Plaza, Houston, TX 77030 USA

[3] Baylor Coll Med, Dept Neurosci, One Baylor Plaza, Houston, TX 77030 USA

[4] Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London SE1 1UL, England

[5] Czech Acad Sci, Inst Microbiol, Prague, Czech Republic

[6] Leibniz Inst Nat Prod Res & Infect Biol Hans Knoel, Dept Microbial Pathogen Mech, D-07737 Jena, Germany

[7] Baylor Coll Med, Natl Sch Trop Med, One Baylor Plaza, Houston, TX 77030 USA

[8] Baylor Coll Med, Dept Pathol & Immunol, One Baylor Plaza, Houston, TX 77030 USA

[9] Baylor Coll Med, Biol Inflammat Ctr, One Baylor Plaza, Houston, TX 77030 USA

[10] Michael E DeBakey VA Ctr Translat Res Inflammatory, Ctr Translat Res Inflammatory Dis, Houston, TX 77030 USA

[11] Baylor Coll Med, Huffington Ctr Aging, One Baylor Plaza, Houston, TX 77030 USA

[12] Friedrich Schiller Univ, Inst Microbiol, D-07737 Jena, Germany

来源：

CELL REPORTS | 2023年 / 42卷 / 10期

基金：

英国惠康基金;

关键词：

SECRETED ASPARTIC PROTEINASES; CENTRAL-NERVOUS-SYSTEM; ALLERGIC RESPONSES; FUNGAL-INFECTION; BRAIN; TISSUE; IDENTIFICATION; RECOGNITION; ASTROCYTES; GENERATION;

D O I：

10.1016/j.celrep.2023.113240

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The fungal pathogen Candida albicans is linked to chronic brain diseases such as Alzheimer's disease (AD), but the molecular basis of brain anti-Candida immunity remains unknown. We show that C. albicans enters the mouse brain from the blood and induces two neuroimmune sensing mechanisms involving secreted as-partic proteinases (Saps) and candidalysin. Saps disrupt tight junction proteins of the blood-brain barrier (BBB) to permit fungal brain invasion. Saps also hydrolyze amyloid precursor protein (APP) into amyloid D (AD)-like peptides that bind to Toll-like receptor 4 (TLR4) and promote fungal killing in vitro while candidalysin engages the integrin CD11b (Mac-1) on microglia. Recognition of AD-like peptides and candidalysin pro-motes fungal clearance from the brain, and disruption of candidalysin recognition through CD11b markedly prolongs C. albicans cerebral mycosis. Thus, C. albicans is cleared from the brain through innate immune mechanisms involving Saps, AD, candidalysin, and CD11b.

引用

页数：19

共 50 条

[1] LPS activation of Toll-like receptor 4 signals CD11b/CD18 expression in neutrophils
Zhou, XM
Gao, XP
Fan, J
Liu, QH
Anwar, KN
Frey, RS
Malik, AB
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2005, 288 (04) : L655 - L662
[2] Neutrophil and monocyte toll-like receptor 4, CD11b and reactive oxygen intermediates, and neuroimaging outcomes in preterm infants
O'Hare, Fiona M.
Watson, William
O'Neill, Amanda
Grant, Tim
Onwuneme, Chike
Donoghue, Veronica
Mooney, Eoghan
Downey, Paul
Murphy, John
Twomey, Anne
Molloy, Eleanor J.
PEDIATRIC RESEARCH, 2015, 78 (01) : 82 - 90
[3] Neutrophil and monocyte toll-like receptor 4, CD11b and reactive oxygen intermediates, and neuroimaging outcomes in preterm infants
Fiona M. O’Hare
William Watson
Amanda O’Neill
Tim Grant
Chike Onwuneme
Veronica Donoghue
Eoghan Mooney
Paul Downey
John Murphy
Anne Twomey
Eleanor J. Molloy
Pediatric Research, 2015, 78 : 82 - 90
[4] Toll-Like Receptor Induced CD11b and L-Selectin Response in Patients with Coronary Artery Disease
Elsenberg, Ellen H. A. M.
Hillaert, Marieke A.
den Ruijter, Hester M.
Sels, Jan-Willem E. M.
Scholtes, Vincent P. W.
Nathoe, Hendrik M.
Kuiper, Johan
Jukema, J. Wouter
Doevendans, Pieter A.
Pasterkamp, Gerard
Hoefer, Imo E.
PLOS ONE, 2013, 8 (04):
[5] Lymphocytes utilize CD11b/CD18 for adhesion to Candida albicans
Forsyth, CB
Mathews, HL
CELLULAR IMMUNOLOGY, 1996, 170 (01) : 91 - 100
[6] Function and Phenotype of Microglia Are Determined by Toll-Like Receptor 2/Toll-Like Receptor 4 Activation Sequence
Li, Weixin
Gao, Guodong
Guo, Qingdong
Jia, Dong
Wang, Julei
Wang, Xuelian
He, Shiming
Liang, Qinchuan
DNA AND CELL BIOLOGY, 2009, 28 (10) : 493 - 499
[7] Candida albicans allergenic extract stimulates expression of toll-like receptor 2 and toll-like receptor 9 and increases expression of toll-like receptor 8 in human polymorphonuclear leukocytes
Signore, R
Romani, L
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, 2005, 52 (03) : P7 - P7
[8] Role of microglia and toll-like receptor 4 in the pathophysiology of delirium
Jalleh, Ryan
Koh, Keith
Choi, Boyoun
Liu, Ebony
Maddison, John
Hutchinson, Mark R.
MEDICAL HYPOTHESES, 2012, 79 (06) : 735 - 739
[9] The role of Toll-like receptor-4 for host defense against disseminated Candida albicans infection
Kullberg, BJ
Netea, MG
Van der Graaf, CA
Vonk, A
Van der Meer, JW
CLINICAL INFECTIOUS DISEASES, 2001, 33 (07) : 1195 - 1195
[10] Role of the toll-like receptor 4 Asp299Gly polymorphism in susceptibility to Candida albicans infection
Morré, SA
Murillo, LS
Spaargaren, J
Fennema, HSA
Peña, AS
JOURNAL OF INFECTIOUS DISEASES, 2002, 186 (09): : 1377 - 1379

← 1 2 3 4 5 →