A Tick Mannose-Binding Lectin Inhibitor Interferes with the Vertebrate Complement Cascade to Enhance Transmission of the Lyme Disease Agent

Schuijt, Tim J.; Coumou, Jeroen; Narasimhan, Sukanya; Dai, Jianfeng; DePonte, Kathleen; Wouters, Diana; Brouwer, Mieke C.; Oei, Arlene L.; Roelofs, Joris J. T. H.; Dam, Alje P. van; Poll, Tom van der; Veer, Cornelis van ’t; Hovius, Joppe W.; Fikrig, Erol

doi:10.1016/j.chom.2011.06.010

Cited by 146 publications

(198 citation statements)

References 31 publications

Supporting

Mentioning

195

Contrasting

Order By: Relevance

“…Many studies have identified CTLs as an important family of pattern recognition receptors (PRRs) that are involved in the induction of innate immunity gene expression in response to pathogen invasion in vertebrates (16,19). Response signaling is primed after glycan recognition and binding by CTLs (20)(21)(22)(23)(24). However, during flavivirus infection in mammals and insects, certain CTLs are recruited to facilitate infection.…”

mentioning

confidence: 99%

mosGCTL-7, a C-Type Lectin Protein, Mediates Japanese Encephalitis Virus Infection in Mosquitoes

Liu

Qian

Jung

et al. 2017

J Virol

View full text Add to dashboard Cite

Japanese encephalitis virus (JEV) is an arthropod-borne flavivirus prevalent in Asia and the Western Pacific and is the leading cause of viral encephalitis. JEV is maintained in a transmission cycle between mosquitoes and vertebrate hosts, but the molecular mechanisms by which the mosquito vector participates in transmission are unclear. We investigated the expression of all C-type lectins during JEV infection in Aedes aegypti. The C-type lectin mosquito galactose-specific C-type lectin 7 (mosGCTL-7) (VectorBase accession no. AAEL002524) was significantly upregulated by JEV infection and facilitated infection in vivo and in vitro. mosGCTL-7 bound to the N-glycan at N154 on the JEV envelope protein. This recognition of viral N-glycan by mosGCTL-7 is required for JEV infection, and we found that this interaction was Ca 2ϩ dependent. After mosGCTL-7 bound to the glycan, mosPTP-1 bound to mosGCTL-7, promoting JEV entry. The viral burden in vivo and in vitro was significantly decreased by mosPTP-1 double-stranded RNA (dsRNA) treatment, and infection was abolished by anti-mosGCTL-7 antibodies. Our results indicate that the mosGCTL-7/mosPTP-1 pathway plays a key role in JEV infection in mosquitoes. An improved understanding of the mechanisms underlying flavivirus infection in mosquitoes will provide further opportunities for developing new strategies to control viral dissemination in nature.IMPORTANCE Japanese encephalitis virus is a mosquito-borne flavivirus and is the primary cause of viral encephalitis in the Asia-Pacific region. Twenty-four countries in the WHO Southeast Asia and Western Pacific regions have endemic JEV transmission, which exposes Ͼ3 billion people to the risks of infection, although JEV primarily affects children. C-type lectins are host factors that play a role in flavivirus infection in humans, swine, and other mammals. In this study, we investigated C-type lectin functions in JEV-infected Aedes aegypti and Culex pipiens pallens mosquitoes and cultured cells. JEV infection changed the expression of almost all C-type lectins in vivo and in vitro, and mosGCTL-7 bound to the JEV envelope protein via an N-glycan at N154. Cell surface mosPTP-1 interacted with the mosGCTL-7-JEV complex to facilitate virus infection in vivo and in vitro. Our findings provide further opportunities for developing new strategies to control arbovirus dissemination in nature.

show abstract

mentioning

confidence: 99%

mosGCTL-7, a C-Type Lectin Protein, Mediates Japanese Encephalitis Virus Infection in Mosquitoes

Liu

Qian

Jung

et al. 2017

J Virol

View full text Add to dashboard Cite

show abstract

“…Third, because the borrelia-expressed ligand that interacts with MBL has not been identified and because LB in Europe is caused mainly by B. garinii and B. afzelii, a similar study should be performed in the United States to investigate whether deficient MBL pathway of the complement cascade also is a risk factor in patients in an area in which B. burgdorferi sensu stricto is the only encountered genospecies. However, the study that revealed the essential role of the MBL pathway in the eradication of borrelia was performed with B. burgdorferi sensu stricto, which suggests that similar results would be obtained in the United States (7).…”

Section: Discussionmentioning

confidence: 79%

“…It was recently revealed that the tick salivary lectin pathway inhibitor effectively inhibits the binding of MBL to its ligand at the tick bite site, thereby interfering with complement-mediated killing of borrelia (7,8). This finding highlights the importance of MBLmediated protection against LB.…”

Section: Yme Borreliosis (Lb) Is the Most Common Pathogenic Tick-mentioning

confidence: 90%

Lyme Borreliosis and Deficient Mannose-Binding Lectin Pathway of Complement

Sajanti

Gröndahl-Yli-Hannuksela

Kauko

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

Risk factors for the widely endemic and much-debated tick-borne infection, Lyme borreliosis (LB), are unknown. The mannose-binding lectin (MBL) pathway of the complement cascade has an essential role in the eradication of Borrelia burgdorferi. A sufficient concentration of biologically active MBL in body fluids is an indicator of proper function of the MBL pathway. In this study, we investigated whether impaired MBL pathway function, represented by reduced serum MBL concentration, predisposes individuals to LB. First, we determined a serum MBL concentration cut-off level associated with diminished MBL pathway function in a group of 201 individuals. Then, we identified 350 borrelia Ab+ LB patient serum samples and 350 Ab− control samples from the archives of our laboratory and measured serum MBL concentrations in both sample groups. The concentration data were analyzed statistically using logistic regression, controlling for MBL cut-off, age, gender, and age and gender interaction. Serum MBL concentrations < 787 and < 445 ng/ml were associated with diminished and deficient MBL pathway function, respectively. Using these cut-offs, diminished (41.4 versus 27.4%, p = 0.0027) and deficient (26.3 versus 17.1%, p = 0.0361) MBL pathway functions were observed statistically more frequently in the LB patient samples than in the control samples. Also, the age-adjusted median serum MBL concentrations were significantly lower in the LB patient samples than in the non-LB controls. Our findings indicate that a deficiency in the MBL pathway of the complement cascade is a risk factor for developing disseminated Ab+ LB.

show abstract

“…Proteins of the Salp15-like multigenic family are produced in the tick salivary glands and bind to Borrelia spirochetes to modulate host immunity, thus facilitating infection of the host [13,14]. Tick saliva secreted into the host suppresses local host immune responses, primarily to enable blood acquisition; however, the resulting host immunosuppression facilitates host infection [15-18]. Since tick salivary secretions are the main mediators of host immunosuppression or immunomodulation, salivary composition plays a critical role in tick-borne pathogen transmission and represents a major topic of interest to researchers in the field [3].…”

Section: Ticks Hosts and Pathogensmentioning

confidence: 99%

Sialomes and Mialomes: A Systems-Biology View of Tick Tissues and Tick–Host Interactions

Chmelař

Kotál

Karim

et al. 2016

Trends in Parasitology

107

116

View full text Add to dashboard Cite

Tick saliva facilitates tick feeding and infection of the host. Gene expression analysis of tick salivary glands and other tissues involved in host-pathogen interactions has revealed a wide range of bioactive tick proteins. Transcriptomic analysis has been a milestone in the field and has recently been enhanced by next generation sequencing. Furthermore, the application of quantitative proteomics to ticks with unknown genomes has provided deeper insights into the molecular mechanisms underlying tick hematophagy, pathogen transmission, and tick-host-pathogen interactions. Here we review current knowledge on the transcriptomics and proteomics of tick tissues from a systems biology perspective and discuss future challenges in the field.

show abstract

A Tick Mannose-Binding Lectin Inhibitor Interferes with the Vertebrate Complement Cascade to Enhance Transmission of the Lyme Disease Agent

Cited by 146 publications

References 31 publications

mosGCTL-7, a C-Type Lectin Protein, Mediates Japanese Encephalitis Virus Infection in Mosquitoes

mosGCTL-7, a C-Type Lectin Protein, Mediates Japanese Encephalitis Virus Infection in Mosquitoes

Lyme Borreliosis and Deficient Mannose-Binding Lectin Pathway of Complement

Sialomes and Mialomes: A Systems-Biology View of Tick Tissues and Tick–Host Interactions

Contact Info

Product

Resources

About