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CRIg plays an essential role in intravascular clearance of bloodborne parasites by interacting with complement.

ABSTRACT: Although CRIg was originally identified as a macrophage receptor for binding complement C3b/iC3b in vitro, recent studies reveal that CRIg functions as a pattern recognition receptor in vivo for Kupffer cells (KCs) to directly bind bacterial pathogens in a complement-independent manner. This raises the critical question of whether CRIg captures circulating pathogens through interactions with complement in vivo under flow conditions. Furthermore, the role of CRIg during parasitic infection is unknown. Taking advantage of intravital microscopy and using African trypanosomes as a model, we studied the role of CRIg in intravascular clearance of bloodborne parasites. Complement C3 is required for intravascular clearance of African trypanosomes by KCs, preventing the early mortality of infected mice. Moreover, antibodies are essential for complement-mediated capture of circulating parasites by KCs. Interestingly, reduced antibody production was observed in the absence of complement C3 during infection. We further demonstrate that CRIg but not CR3 is critically involved in KC-mediated capture of circulating parasites, accounting for parasitemia control and host survival. Of note, CRIg cannot directly catch circulating parasites and antibody-induced complement activation is indispensable for CRIg-mediated parasite capture. Thus, we provide evidence that CRIg, by interacting with complement in vivo, plays an essential role in intravascular clearance of bloodborne parasites. Targeting CRIg may be considered as a therapeutic strategy.

SUBMITTER: Liu G

PROVIDER: S-EPMC6883839 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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CRIg plays an essential role in intravascular clearance of bloodborne parasites by interacting with complement.

Liu Gongguan G Fu Yong Y Yosri Mohammed M Chen Yanli Y Sun Peng P Xu Jinjun J Zhang Mingshun M Sun Donglei D Strickland Ashley B AB Mackey Zachary B ZB Shi Meiqing M

Proceedings of the National Academy of Sciences of the United States of America 20191113 48

Although CRIg was originally identified as a macrophage receptor for binding complement C3b/iC3b in vitro, recent studies reveal that CRIg functions as a pattern recognition receptor in vivo for Kupffer cells (KCs) to directly bind bacterial pathogens in a complement-independent manner. This raises the critical question of whether CRIg captures circulating pathogens through interactions with complement in vivo under flow conditions. Furthermore, the role of CRIg during parasitic infection is unk ...[more]

PMID: 31723045

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Dataset Information

CRIg plays an essential role in intravascular clearance of bloodborne parasites by interacting with complement.

Publications

CRIg plays an essential role in intravascular clearance of bloodborne parasites by interacting with complement.

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