Aedes Mosquito Salivary Components and Their Effect on the Immune Response to Arboviruses

Guerrero, David; Cantaert, Tineke; Missé, Dorothée

doi:10.3389/fcimb.2020.00407

Cited by 45 publications

(55 citation statements)

References 101 publications

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“…After 3 days of rest in a humid chamber at laboratory temperature, ticks were fed on C3H/HeN mice (15-20 nymphs per mouse) until full engorgement. Two weeks later, mice were sacrificed, and the numbers of Borrelia spirochetes in the earlobe, urinary bladder, heart tissue, and ankle joint were estimated by qPCR [82] and normalized to the number of mouse genomes [83] (primer and probe sequences in Supplementary Table S1). The level of gene knockdown was checked by qPCR in an independent experiment.…”

Section: Rna Silencing and Borrelia Transmissionmentioning

confidence: 99%

Ixodes ricinus Salivary Serpin Iripin-8 Inhibits the Intrinsic Pathway of Coagulation and Complement

Kotál

Polderdijk

Langhansová

et al. 2021

IJMS

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Tick saliva is a rich source of antihemostatic, anti-inflammatory, and immunomodulatory molecules that actively help the tick to finish its blood meal. Moreover, these molecules facilitate the transmission of tick-borne pathogens. Here we present the functional and structural characterization of Iripin-8, a salivary serpin from the tick Ixodes ricinus, a European vector of tick-borne encephalitis and Lyme disease. Iripin-8 displayed blood-meal-induced mRNA expression that peaked in nymphs and the salivary glands of adult females. Iripin-8 inhibited multiple proteases involved in blood coagulation and blocked the intrinsic and common pathways of the coagulation cascade in vitro. Moreover, Iripin-8 inhibited erythrocyte lysis by complement, and Iripin-8 knockdown by RNA interference in tick nymphs delayed the feeding time. Finally, we resolved the crystal structure of Iripin-8 at 1.89 Å resolution to reveal an unusually long and rigid reactive center loop that is conserved in several tick species. The P1 Arg residue is held in place distant from the serpin body by a conserved poly-Pro element on the P′ side. Several PEG molecules bind to Iripin-8, including one in a deep cavity, perhaps indicating the presence of a small-molecule binding site. This is the first crystal structure of a tick serpin in the native state, and Iripin-8 is a tick serpin with a conserved reactive center loop that possesses antihemostatic activity that may mediate interference with host innate immunity.

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Section: Rna Silencing and Borrelia Transmissionmentioning

confidence: 99%

Ixodes ricinus Salivary Serpin Iripin-8 Inhibits the Intrinsic Pathway of Coagulation and Complement

Kotál

Polderdijk

Langhansová

et al. 2021

IJMS

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“…It is suggested that mosquito bite enhancement of virus infection is not related to interferon response suppression. Instead, host increased susceptibility is closely related to neutrophil-dependent inflammation after a bite [ 82 , 83 ]. Following a bite, mast cell degranulation markedly increases the expression of IL-1β, IL-6 and neutrophil-attracting chemokines such as CXCL1, CXCL2, CXCL3 and CXCL5.…”

Section: Participation Of Neutrophils and Neutrophil-associated Molecules In Flaviviral Diseasesmentioning

confidence: 99%

Neutrophil Recruitment and Participation in Severe Diseases Caused by Flavivirus Infection

Fontoura

Rocha

Marques

2021

Life

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Neutrophils are first-line responders to infections and are recruited to target tissues through the action of chemoattractant molecules, such as chemokines. Neutrophils are crucial for the control of bacterial and fungal infections, but their role in the context of viral infections has been understudied. Flaviviruses are important human viral pathogens transmitted by arthropods. Infection with a flavivirus may result in a variety of complex disease manifestations, including hemorrhagic fever, encephalitis or congenital malformations. Our understanding of flaviviral diseases is incomplete, and so is the role of neutrophils in such diseases. Here we present a comprehensive overview on the participation of neutrophils in severe disease forms evolving from flavivirus infection, focusing on the role of chemokines and their receptors as main drivers of neutrophil function. Neutrophil activation during viral infection was shown to interfere in viral replication through effector functions, but the resulting inflammation is significant and may be detrimental to the host. For congenital infections in humans, neutrophil recruitment mediated by CXCL8 would be catastrophic. Evidence suggests that control of neutrophil recruitment to flavivirus-infected tissues may reduce immunopathology in experimental models and patients, with minimal loss to viral clearance. Further investigation on the roles of neutrophils in flaviviral infections may reveal unappreciated functions of this leukocyte population while increasing our understanding of flaviviral disease pathogenesis in its multiple forms.

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“…This route of pathogen transmission is vastly different from the vector-mediated natural infection and may lead to erroneous results of challenge studies. In comparison with other vector-borne disease models, studies of mosquito-borne and tick-borne diseases suggested that the needle-based transmission route does not fully recapitulate vector-mediated transmission, due to the absence of important immunomodulatory molecules contained in vector saliva [ 37 , 38 ] or by bypassing the natural route of host cell invasion which alters the resulting host immune response. Utilization of needle-based inoculation approach potentially leads to incomparable results to the vector-mediated transmission and immunological response observed in humans [ 39 , 40 , 41 , 42 ].…”

Section: Introductionmentioning

confidence: 99%

Establishment of a Rhesus Macaque Model for Scrub Typhus Transmission: Pilot Study to Evaluate the Minimal Orientia tsutsugamushi Transmission Time by Leptotrombidium chiangraiensis Chiggers

et al. 2021

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Recently, an intradermal inoculation of the rhesus macaque model of scrub typhus has been characterized at our institution. The current project was to establish a rhesus macaque model of scrub typhus using the naturally infected chigger challenge method that faithfully mimics the natural route of pathogen transmission to fully understand the host-pathogen-vector interactions influencing pathogen transmission. Unlike the needle-based inoculation route, Orientia tsutsugamushi-infected chiggers introduce both pathogen and chigger saliva into the host epidermis at the bite site. However, information on the interaction or influence of chigger saliva on pathogenesis and immunity of host has been limited, consequently hindering vaccine development and transmission-blocking studies. To characterize chigger inoculated O. tsutsugamushi in rhesus macaques, we determined the minimum chigger attachment time required to efficiently transmit O. tsutsugamushi to the immunocompetent hosts and preliminary assessed clinical parameters, course of bacterial infection, and host’s immunological response to identifying potential factors influencing pathogen infection. Chigger infestation on hosts resulted in: (i) Rapid transmission of O. tsutsugamushi within 1 h and (ii) antigen-specific type I and II T-cell responses were markedly increased during the acute phase of infection, suggesting that both systems play critical roles in response to the pathogen control during the primary infection. In summary, we demonstrate that O. tsutsugamushi infection in rhesus macaques via chigger challenge recapitulates the time of disease onset and bacteremia observed in scrub typhus patients. Levels of proinflammatory cytokines and chemokines were positively correlated with bacteremia.

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Aedes Mosquito Salivary Components and Their Effect on the Immune Response to Arboviruses

Cited by 45 publications

References 101 publications

Ixodes ricinus Salivary Serpin Iripin-8 Inhibits the Intrinsic Pathway of Coagulation and Complement

Ixodes ricinus Salivary Serpin Iripin-8 Inhibits the Intrinsic Pathway of Coagulation and Complement

Neutrophil Recruitment and Participation in Severe Diseases Caused by Flavivirus Infection

Establishment of a Rhesus Macaque Model for Scrub Typhus Transmission: Pilot Study to Evaluate the Minimal Orientia tsutsugamushi Transmission Time by Leptotrombidium chiangraiensis Chiggers

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