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Role of early lectin pathway activation in the complement-mediated killing of Trypanosoma cruzi. / Cestari, Igor dos S; Krarup, Anders; Sim, Robert B; Inal, Jameel M; Ramirez, Marcel I.

In: Molecular immunology, Vol. 47, No. 2-3, 27.08.2009, p. 426-37.

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Cestari, Igor dos S ; Krarup, Anders ; Sim, Robert B ; Inal, Jameel M ; Ramirez, Marcel I. / Role of early lectin pathway activation in the complement-mediated killing of Trypanosoma cruzi. In: Molecular immunology. 2009 ; Vol. 47, No. 2-3. pp. 426-37.

Bibtex

@article{7519b3bca5a54314b0519c6775a4252e,
title = "Role of early lectin pathway activation in the complement-mediated killing of Trypanosoma cruzi",
abstract = "The complement system is the first line of defence against pathogen infection and can be activated by the classic, alternative and lectin pathways. Trypanosoma cruzi, the causative agent of Chagas disease, has to evade complement system killing and invade the host cells to progress in infection. T. cruzi infectious stages resist complement-mediated killing by expressing surface receptors, which dissociate or prevent C3 convertase formation. Here, we present the first evidence that T. cruzi activates the complement lectin pathway. We detected rapid binding of mannan-binding lectin, H-ficolin, and L-ficolin to the surface of T. cruzi, and found that serum depleted of these molecules failed to kill parasites. Furthermore, lectin pathway activation by T. cruzi required the MBL-associated serine protease 2 (MASP2) activity resulting in C2 factor cleavage. In addition, we demonstrate that the infectious stage of T. cruzi inhibits the lectin pathway activation and complement killing expressing the complement C2 receptor inhibitor trispanning (CRIT) protein. Transgenic parasites overexpressing CRIT were highly resistant to complement-mediated killing. CRIT-derived peptides inhibited both C2 binding to the surface of T. cruzi and parasite killing. Biochemical studies revealed that the CRIT extracellular domain 1 inhibits MASP2 cleavage of C2 factor and thereby impairs C3 convertase formation. Our findings establish that the complement lectin pathway recognizes T. cruzi and provide molecular insights into how the infectious stage inhibits this activation to resist complement system killing.",
keywords = "Animals, Cell Death, Cell Membrane, Complement C2, Complement C4, Complement Pathway, Mannose-Binding Lectin, Glycosylation, Humans, Lectins, Life Cycle Stages, Mannose-Binding Lectin, Mannose-Binding Protein-Associated Serine Proteases, Polysaccharides, Protein Binding, Protein Structure, Tertiary, Receptors, Cell Surface, Recombinant Proteins, Serum, Trypanosoma cruzi, Journal Article, Research Support, Non-U.S. Gov't",
author = "Cestari, {Igor dos S} and Anders Krarup and Sim, {Robert B} and Inal, {Jameel M} and Ramirez, {Marcel I}",
year = "2009",
month = "8",
day = "27",
doi = "10.1016/j.molimm.2009.08.030",
language = "English",
volume = "47",
pages = "426--37",
journal = "Molecular immunology",
issn = "0161-5890",
publisher = "Elsevier Ltd",
number = "2-3",

}

RIS

TY - JOUR

T1 - Role of early lectin pathway activation in the complement-mediated killing of Trypanosoma cruzi

AU - Cestari, Igor dos S

AU - Krarup, Anders

AU - Sim, Robert B

AU - Inal, Jameel M

AU - Ramirez, Marcel I

PY - 2009/8/27

Y1 - 2009/8/27

N2 - The complement system is the first line of defence against pathogen infection and can be activated by the classic, alternative and lectin pathways. Trypanosoma cruzi, the causative agent of Chagas disease, has to evade complement system killing and invade the host cells to progress in infection. T. cruzi infectious stages resist complement-mediated killing by expressing surface receptors, which dissociate or prevent C3 convertase formation. Here, we present the first evidence that T. cruzi activates the complement lectin pathway. We detected rapid binding of mannan-binding lectin, H-ficolin, and L-ficolin to the surface of T. cruzi, and found that serum depleted of these molecules failed to kill parasites. Furthermore, lectin pathway activation by T. cruzi required the MBL-associated serine protease 2 (MASP2) activity resulting in C2 factor cleavage. In addition, we demonstrate that the infectious stage of T. cruzi inhibits the lectin pathway activation and complement killing expressing the complement C2 receptor inhibitor trispanning (CRIT) protein. Transgenic parasites overexpressing CRIT were highly resistant to complement-mediated killing. CRIT-derived peptides inhibited both C2 binding to the surface of T. cruzi and parasite killing. Biochemical studies revealed that the CRIT extracellular domain 1 inhibits MASP2 cleavage of C2 factor and thereby impairs C3 convertase formation. Our findings establish that the complement lectin pathway recognizes T. cruzi and provide molecular insights into how the infectious stage inhibits this activation to resist complement system killing.

AB - The complement system is the first line of defence against pathogen infection and can be activated by the classic, alternative and lectin pathways. Trypanosoma cruzi, the causative agent of Chagas disease, has to evade complement system killing and invade the host cells to progress in infection. T. cruzi infectious stages resist complement-mediated killing by expressing surface receptors, which dissociate or prevent C3 convertase formation. Here, we present the first evidence that T. cruzi activates the complement lectin pathway. We detected rapid binding of mannan-binding lectin, H-ficolin, and L-ficolin to the surface of T. cruzi, and found that serum depleted of these molecules failed to kill parasites. Furthermore, lectin pathway activation by T. cruzi required the MBL-associated serine protease 2 (MASP2) activity resulting in C2 factor cleavage. In addition, we demonstrate that the infectious stage of T. cruzi inhibits the lectin pathway activation and complement killing expressing the complement C2 receptor inhibitor trispanning (CRIT) protein. Transgenic parasites overexpressing CRIT were highly resistant to complement-mediated killing. CRIT-derived peptides inhibited both C2 binding to the surface of T. cruzi and parasite killing. Biochemical studies revealed that the CRIT extracellular domain 1 inhibits MASP2 cleavage of C2 factor and thereby impairs C3 convertase formation. Our findings establish that the complement lectin pathway recognizes T. cruzi and provide molecular insights into how the infectious stage inhibits this activation to resist complement system killing.

KW - Animals

KW - Cell Death

KW - Cell Membrane

KW - Complement C2

KW - Complement C4

KW - Complement Pathway, Mannose-Binding Lectin

KW - Glycosylation

KW - Humans

KW - Lectins

KW - Life Cycle Stages

KW - Mannose-Binding Lectin

KW - Mannose-Binding Protein-Associated Serine Proteases

KW - Polysaccharides

KW - Protein Binding

KW - Protein Structure, Tertiary

KW - Receptors, Cell Surface

KW - Recombinant Proteins

KW - Serum

KW - Trypanosoma cruzi

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.molimm.2009.08.030

DO - 10.1016/j.molimm.2009.08.030

M3 - Article

VL - 47

SP - 426

EP - 437

JO - Molecular immunology

JF - Molecular immunology

SN - 0161-5890

IS - 2-3

ER -