Dataset Information

Myeloid C-Type Lectin Receptors in Tuberculosis and HIV Immunity: Insights Into Co-infection?

ABSTRACT: C-type lectin receptors (CLRs) are carbohydrate binding pattern recognition receptors (PRRs) which play a central role in host recognition of pathogenic microorganisms. Signaling through CLRs displayed on antigen presenting cells dictates important innate and adaptive immune responses. Several pathogens have evolved mechanisms to exploit the receptors or signaling pathways of the CLR system to gain entry or propagate in host cells. CLR responses to high priority pathogens such as Mycobacterium tuberculosis (Mtb), HIV, Ebola, and others are described and considered potential avenues for therapeutic intervention. Mtb and HIV are the leading causes of death due to infectious disease and have a synergistic relationship that further promotes aggressive disease in co-infected persons. Immune recognition through CLRs and other PRRs are important determinants of disease outcomes for both TB and HIV. Investigations of CLR responses to Mtb and HIV, to date, have primarily focused on single infection outcomes and do not account for the potential effects of co-infection. This review will focus on CLRs recognition of Mtb and HIV motifs. We will describe their respective roles in protective immunity and immune evasion or exploitation, as well as their potential as genetic determinants of disease susceptibility, and as avenues for development of therapeutic interventions. The potential convergence of CLR-driven responses of the innate and adaptive immune systems in the setting of Mtb and HIV co-infection will further be discussed relevant to disease pathogenesis and development of clinical interventions.

SUBMITTER: Naqvi KF

PROVIDER: S-EPMC7283559 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Myeloid C-Type Lectin Receptors in Tuberculosis and HIV Immunity: Insights Into Co-infection?

Naqvi Kubra F KF Endsley Janice J JJ

Frontiers in cellular and infection microbiology 20200603

C-type lectin receptors (CLRs) are carbohydrate binding pattern recognition receptors (PRRs) which play a central role in host recognition of pathogenic microorganisms. Signaling through CLRs displayed on antigen presenting cells dictates important innate and adaptive immune responses. Several pathogens have evolved mechanisms to exploit the receptors or signaling pathways of the CLR system to gain entry or propagate in host cells. CLR responses to high priority pathogens such as <i>Mycobacteriu ...[more]

PMID: 32582566

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Project description:Mannose-binding lectin (MBL) is a key soluble effector of the innate immune system that recognizes pathogen-specific surface glycans. Surprisingly, low-producing MBL genetic variants that may predispose children and immunocompromised individuals to infectious diseases are more common than would be expected in human populations. Since certain immune defense molecules, such as immunoglobulins, can be exploited by invasive pathogens, we hypothesized that MBL might also enhance infections in some circumstances. Consequently, the low and intermediate MBL levels commonly found in human populations might be the result of balancing selection. Using model infection systems with pseudotyped and authentic glycosylated viruses, we demonstrated that MBL indeed enhances infection of Ebola, Hendra, Nipah and West Nile viruses in low complement conditions. Mechanistic studies with Ebola virus (EBOV) glycoprotein pseudotyped lentiviruses confirmed that MBL binds to N-linked glycan epitopes on viral surfaces in a specific manner via the MBL carbohydrate recognition domain, which is necessary for enhanced infection. MBL mediates lipid-raft-dependent macropinocytosis of EBOV via a pathway that appears to require less actin or early endosomal processing compared with the filovirus canonical endocytic pathway. Using a validated RNA interference screen, we identified C1QBP (gC1qR) as a candidate surface receptor that mediates MBL-dependent enhancement of EBOV infection. We also identified dectin-2 (CLEC6A) as a potentially novel candidate attachment factor for EBOV. Our findings support the concept of an innate immune haplotype that represents critical interactions between MBL and complement component C4 genes and that may modify susceptibility or resistance to certain glycosylated pathogens. Therefore, higher levels of native or exogenous MBL could be deleterious in the setting of relative hypocomplementemia which can occur genetically or because of immunodepletion during active infections. Our findings confirm our hypothesis that the pressure of infectious diseases may have contributed in part to evolutionary selection of MBL mutant haplotypes.

Dataset Information

Myeloid C-Type Lectin Receptors in Tuberculosis and HIV Immunity: Insights Into Co-infection?

Publications

Myeloid C-Type Lectin Receptors in Tuberculosis and HIV Immunity: Insights Into Co-infection?

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