Immunological consequences of arthropod vector‐derived salivary factors

Abstract

Diseases, such as malaria, dengue, leishmaniasis and tick‐borne encephalitis, affect a substantial percentage of the world's population and continue to result in significant morbidity and mortality. One common aspect of these diseases is that the pathogens that cause them are transmitted by the bite of an infected arthropod (e.g. mosquito, sand fly, tick). The pathogens are delivered into the skin of the mammalian host along with arthropod saliva, which contains a wide variety of bioactive molecules. These saliva components are capable of altering hemostasis and immune responses and may contribute to the ability of the pathogen to establish an infection. The biological and immunological events that occur during pathogen transmission are poorly understood but may hold the key to novel approaches to prevent transmission and/or infection. In May 2011, the National Institute of Allergy and Infectious Diseases (NIAID) of the US National Institutes of Health (NIH) in the Department of Health and Human Services hosted a workshop entitled Immunological Consequences of Vector‐Derived Factors which brought together experts in skin immunology, parasitology and vector biology to outline the gaps in our understanding of the process of pathogen transmission, to explore new approaches to control pathogen transmission, and to initiate and foster multidisciplinary collaborations among these investigators.

Induction of Fas Mediated Caspase-8 Independent Apoptosis in Immune Cells by Armigeres subalbatus Saliva

“…However, less is known about the interaction of saliva with disease processes. Accumulated evidence suggests that mosquito saliva might engage the host immune system that indirectly favours disease establishment [9], [10]. Salivary gland extract (SGE) of the female Ae.…”

Role of immune cell subsets in the establishment of vector‐borne infections

“…This observation has major implications for the development of vaccines based on saliva proteins since many such vaccines would be recombinant proteins. VAMPs would represent a potentially new class of innate immune receptor ligands involved in the host's response against blood‐feeding arthropods and thus possibly also vector‐borne pathogens. The vector and host microbiome During a previous workshop on the biological effects of vector saliva participants discussed how a host's microbiome—particularly the skin microbiome—can affect its susceptibility to infection with vector‐borne diseases. Significant differences in the susceptibility of germ‐free versu s “dirty” mice to Leishmania infection underscore that ultra‐clean animal facilities that prevent the establishment of a microbiome are not suited for studying vector‐borne pathogen transmission in a natural setting .…”

Infection via mosquito bite alters Zika virus replication kinetics in rhesus macaques

“…Other recent studies of ZIKV infection in nonhuman primates have relied on a variety of 52 doses and routes with varying outcomes. For example, five sc inoculations each containing 1 x 53 10 7 PFU (a 50-fold higher cumulative dose than any other published study) of a Cambodian 54 strain of ZIKV in a pregnant pigtail macaque (Macaca nemestrina) resulted in severe fetal 55 neurodevelopmental abnormalities not seen in other studies using a smaller dose of different 56 ZIKV strains 5 . In rhesus and cynomolgus macaques (Macaca mulatta and Macaca fascicularis, 57 respectively), ZIKV RNA persisted in saliva and seminal fluids for at least three weeks after 58 clearance of the virus from the peripheral blood following sc inoculation with 1 x 10 6 PFU of a 59…”

“…Each of these routes and inoculum doses could modulate viral 23 infection kinetics and viral tissue distribution on their own, but none of them entirely recapitulate 24 vector delivery of the virus. Blood feeding by a mosquito ensures delivery of the virus to an 25 anatomically precise target in the dermis of the skin [8][9][10] . When a mosquito feeds it inserts its 26 mouthparts into the skin and then actively probes within the tissue for blood.…”