Toll-like receptor 4 and macrophage scavenger receptor 1 crosstalk regulates phagocytosis of a fungal pathogen.
Toll-like receptor 4 and macrophage scavenger receptor 1 crosstalk regulates phagocytosis of a fungal pathogen.
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Toll样受体4与巨噬细胞清道夫受体1的相互作用调控对一种真菌病原体的吞噬作用。
DOI：
10.1038/s41467-023-40635-w
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发表时间：
2023-08-14
影响因子：
16.6
通讯作者：
May, Robin C.
中科院分区：
文献类型：
--
作者：
Onyishi, Chinaemerem U.;Desanti, Guillaume E.;Wilkinson, Alex L.;Lara-Reyna, Samuel;Frickel, Eva-Maria;Fejer, Gyorgy;Christophe, Olivier D.;Bryant, Clare E.;Mukhopadhyay, Subhankar;Gordon, Siamon;May, Robin C.
机会性真菌病原体新型隐球菌可导致免疫功能低下患者的致命感染。巨噬细胞是宿主对隐球菌反应的中心，然而，目前还不清楚C。新生儿被巨噬细胞识别和吞噬。在此，我们研究了TLR 4在C.新人类我们发现TLR 4功能的丧失意外地增加了鼠和人巨噬细胞对非调理隐球菌的吞噬作用。在Tlr 4 −/−细胞中观察到的吞噬作用增加，通过用氧化LDL（一种已知的清道夫受体配体）预处理巨噬细胞而受到抑制。清道夫受体，巨噬细胞清道夫受体1（MSR 1）（也称为SR-A1或CD 204）在Tlr 4 −/−巨噬细胞中上调。MSR 1的基因消除导致非调理隐球菌的吞噬作用降低75%，强烈表明它是该病原体的关键非调理剂受体。我们继续表明，MSR 1介导的摄取可能涉及FcγR的多分子信号传导复合物的形成，导致SYK、PI 3 K、p38和ERK 1/2活化，以驱动肌动蛋白重塑和吞噬作用。总之，我们的数据表明TLR 4/MSR 1串扰在C.新人类真菌病原体在感染的早期阶段被巨噬细胞识别和吞噬。在此，Onyishi等人鉴定了Toll样受体4和巨噬细胞清道夫受体1在新型隐球菌摄取的调节中的串扰。
The opportunistic fungal pathogen Cryptococcus neoformans causes lethal infections in immunocompromised patients. Macrophages are central to the host response to cryptococci; however, it is unclear how C. neoformans is recognised and phagocytosed by macrophages. Here we investigate the role of TLR4 in the non-opsonic phagocytosis of C. neoformans. We find that loss of TLR4 function unexpectedly increases phagocytosis of non-opsonised cryptococci by murine and human macrophages. The increased phagocytosis observed in Tlr4−/− cells was dampened by pre-treatment of macrophages with oxidised-LDL, a known ligand of scavenger receptors. The scavenger receptor, macrophage scavenger receptor 1 (MSR1) (also known as SR-A1 or CD204) was upregulated in Tlr4−/− macrophages. Genetic ablation of MSR1 resulted in a 75% decrease in phagocytosis of non-opsonised cryptococci, strongly suggesting that it is a key non-opsonic receptor for this pathogen. We go on to show that MSR1-mediated uptake likely involves the formation of a multimolecular signalling complex involving FcγR leading to SYK, PI3K, p38 and ERK1/2 activation to drive actin remodelling and phagocytosis. Altogether, our data indicate a hitherto unidentified role for TLR4/MSR1 crosstalk in the non-opsonic phagocytosis of C. neoformans. Fungal pathogens are recognised and phagocytosed by macrophages in the early stages of infection. Here, Onyishi et al. identify a crosstalk between Toll Like Receptor 4 and Macrophage Scavenger Receptor 1 in the regulation of Cryptococcus neoformans uptake.
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DOI：
10.4049/jimmunol.1700790
发表时间：
2018-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lim J;Coates CJ;Seoane PI;Garelnabi M;Taylor-Smith LM;Monteith P;Macleod CL;Escaron CJ;Brown GD;Hall RA;May RC
通讯作者：
May RC
影响因子：
11.8
作者：
Heit, Bryan;Kim, Hani;Cosio, Gabriela;Castano, Diana;Collins, Richard;Lowell, Clifford A.;Kain, Kevin C.;Trimble, William S.;Grinstein, Sergio
通讯作者：
Grinstein, Sergio
影响因子：
39.3
作者：
Liu T;Zhang L;Joo D;Sun SC
通讯作者：
Sun SC
DOI：
10.3390/jof4010033
发表时间：
2018-03-07
期刊：
Journal of fungi (Basel, Switzerland)
影响因子：
--
作者：
Campuzano A;Wormley FL
通讯作者：
Wormley FL
清道夫受体A调节对肺隐孢子菌感染的免疫反应。
DOI：
10.4049/jimmunol.1203435
发表时间：
2013-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Qiu Y;Dayrit JK;Davis MJ;Carolan JF;Osterholzer JJ;Curtis JL;Olszewski MA
通讯作者：
Olszewski MA