Trichinella spiralis Calreticulin Binds Human Complement C1q As an Immune Evasion Strategy

Abstract Novel therapies to counteract multidrug-resistant gonorrhea are urgently needed. A unique gonococcal immune evasion strategy involves capping of lipooligosaccharide (LOS) with sialic acid by gonococcal sialyltransferase (Lst), utilizing host-derived CMP-sialic acid (CMP-Neu5Ac in humans). LOS sialylation renders gonococci resistant to complement and cationic peptides, and down-regulates the inflammatory response by engaging siglecs. CMP-sialic acid analogs (CMP-nonulosonates [CMP-NulOs]) such as CMP-Leg5,7Ac2 and CMP-Kdn are also utilized by Lst. Incorporation of these NulO analogs into LOS maintains gonococci susceptible to complement. Intravaginal administration of CMP-Kdn or CMP-Leg5,7Ac2 attenuates gonococcal colonization of mouse vaginas. Here, we identify a key mechanism of action for the efficacy of CMP-NulOs. Surprisingly, CMP-NulOs remained effective in complement C1q-/- and C3-/- mice. LOS Neu5Ac, but not Leg5,7Ac2 or Kdn, conferred resistance to the cathelicidins LL-37 (human) and mouse cathelicidin-related antimicrobial peptide in vitro. CMP-NulOs were ineffective in Camp-/- mice, revealing that cathelicidins largely mediate the efficacy of therapeutic CMP-NulOs.

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Human complement C4 inhibition by dengue virus nonstructural protein NS1: An immune evasion strategy of a reemerging infection

Molecular Immunology ◽

10.1016/j.molimm.2008.08.056 ◽

2008 ◽

Vol 45 (16) ◽

pp. 4114

Author(s):

Panisadee Avirutnan ◽

Richard Hauhart ◽

Soonjeon Youn ◽

Prida Malasit ◽

Michael Diamond ◽

...

Keyword(s):

Dengue Virus ◽

Immune Evasion ◽

Nonstructural Protein ◽

Human Complement ◽

Complement C4 ◽

Evasion Strategy

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Trichinella spiralis Paramyosin Binds Human Complement C1q and Inhibits Classical Complement Activation

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0004310 ◽

2015 ◽

Vol 9 (12) ◽

pp. e0004310 ◽

Cited By ~ 15

Author(s):

Ran Sun ◽

Xi Zhao ◽

Zixia Wang ◽

Jing Yang ◽

Limei Zhao ◽

...

Keyword(s):

Complement Activation ◽

Trichinella Spiralis ◽

Human Complement ◽

Complement C1q ◽

Classical Complement

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Faculty Opinions recommendation of Variola virus immune evasion design: expression of a highly efficient inhibitor of human complement.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1007266.96518 ◽

2002 ◽

Author(s):

John Atkinson

Keyword(s):

Immune Evasion ◽

Variola Virus ◽

Human Complement ◽

Efficient Inhibitor ◽

Highly Efficient

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Correction: Japanese Encephalitis Virus Activates Autophagy as a Viral Immune Evasion Strategy

PLoS ONE ◽

10.1371/annotation/f7dcec2f-ed82-4a31-96c6-2953b421fd92 ◽

2013 ◽

Vol 8 (5) ◽

Author(s):

Rui Jin ◽

Wandi Zhu ◽

Shengbo Cao ◽

Rui Chen ◽

Hui Jin ◽

...

Keyword(s):

Japanese Encephalitis Virus ◽

Japanese Encephalitis ◽

Immune Evasion ◽

Encephalitis Virus ◽

Viral Immune Evasion ◽

Evasion Strategy

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Plasticity in early immune evasion strategies of a bacterial pathogen

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1718595115 ◽

2018 ◽

Vol 115 (16) ◽

pp. E3788-E3797 ◽

Cited By ~ 6

Author(s):

Quentin Bernard ◽

Alexis A. Smith ◽

Xiuli Yang ◽

Juraj Koci ◽

Shelby D. Foor ◽

...

Keyword(s):

Immune Evasion ◽

Bacterial Pathogen ◽

Surface Protein ◽

Innate Immune ◽

Serum Complement ◽

Term Survival ◽

Evasion Strategy ◽

Innate Immune Evasion ◽

Novel Therapeutic

Borrelia burgdorferiis one of the few extracellular pathogens capable of establishing persistent infection in mammals. The mechanisms that sustain long-term survival of this bacterium are largely unknown. Here we report a unique innate immune evasion strategy ofB. burgdorferi, orchestrated by a surface protein annotated as BBA57, through its modulation of multiple spirochete virulent determinants. BBA57 function is critical for early infection but largely redundant for later stages of spirochetal persistence, either in mammals or in ticks. The protein influences host IFN responses as well as suppresses multiple host microbicidal activities involving serum complement, neutrophils, and antimicrobial peptides. We also discovered a remarkable plasticity in BBA57-mediated spirochete immune evasion strategy because its loss, although resulting in near clearance of pathogens at the inoculum site, triggers nonheritable adaptive changes that exclude detectable nucleotide alterations in the genome but incorporate transcriptional reprograming events. Understanding the malleability in spirochetal immune evasion mechanisms that ensures their host persistence is critical for the development of novel therapeutic and preventive approaches to combat long-term infections like Lyme borreliosis.

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Plasminogen Binding Proteins and Plasmin Generation on the Surface ofLeptospiraspp.: The Contribution to the Bacteria-Host Interactions

Journal of Biomedicine and Biotechnology ◽

10.1155/2012/758513 ◽

2012 ◽

Vol 2012 ◽

pp. 1-17 ◽

Cited By ~ 21

Author(s):

Monica L. Vieira ◽

Marina V. Atzingen ◽

Rosane Oliveira ◽

Renata S. Mendes ◽

Renan F. Domingos ◽

...

Keyword(s):

Infectious Disease ◽

Immune Evasion ◽

Host Tissue ◽

Research Groups ◽

Tissue Penetration ◽

Bacterial Surface ◽

Host Interactions ◽

Evasion Strategy ◽

Immune Attack ◽

Human Plasminogen

Leptospirosis is considered a neglected infectious disease of human and veterinary concern. Although extensive investigations on host-pathogen interactions have been pursued by several research groups, mechanisms of infection, invasion and persistence of pathogenicLeptospiraspp. remain to be elucidated. We have reported the ability of leptospires to bind human plasminogen (PLG) and to generate enzimatically active plasmin (PLA) on the bacteria surface. PLA-coatedLeptospiracan degrade immobilized ECM molecules, an activity with implications in host tissue penetration. Moreover, we have identified and characterized several proteins that may act as PLG-binding receptors, each of them competent to generate active plasmin. The PLA activity associated to the outer surface ofLeptospiracould hamper the host immune attack by conferring the bacteria some benefit during infection. The PLA-coated leptospires obstruct complement C3b and IgG depositions on the bacterial surface, most probably through degradation. The decrease of leptospiral opsonization might be an important aspect of the immune evasion strategy. We believe that the presence of PLA on the leptospiral surface may (i) facilitate host tissue penetration, (ii) help the bacteria to evade the immune system and, as a consequence, (iii) permitLeptospirato reach secondary sites of infection.

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