Host immune response to mosquito-transmitted chikungunya virus differs from that elicited by needle inoculated virus.
BACKGROUND
Mosquito-borne diseases are a worldwide public health threat. Mosquitoes transmit viruses or parasites during feeding, along with salivary proteins that modulate host responses to facilitate both blood feeding and pathogen transmission. Understanding these earliest events in mosquito transmission of arboviruses by mosquitoes is essential for development and assessment of rational vaccine and treatment strategies. In this report, we compared host immune responses to chikungunya virus (CHIKV) transmission by (1) mosquito bite, or (2) by needle inoculation.


RESULTS
Differential cytokine expression was measured using quantitative real-time RT-PCR, at sites of uninfected mosquito bites, CHIKV-infected mosquito bites, and needle-inoculated CHIKV. Both uninfected and CHIKV infected mosquitoes polarized host cytokine response to a TH2 profile. Compared to uninfected mosquito bites, expression of IL-4 induced by CHIKV-infected mosquitoes were 150 fold and 527.1 fold higher at 3 hours post feeding (hpf) and 6 hpf, respectively. A significant suppression of TH1 cytokines and TLR-3 was also observed. These significant differences may result from variation in the composition of uninfected and CHIKV-infected mosquito saliva. Needle injected CHIKV induced a robust interferon-gamma, no detectable IL-4, and a significant up-regulation of TLR-3.


CONCLUSIONS
This report describes the first analysis of cutaneous cytokines in mice bitten by CHIKV-infected mosquitoes. Our data demonstrate contrasting immune activation in the response to CHIKV infection by mosquito bite or needle inoculation. The significant role of mosquito saliva in these earliest events of CHIKV transmission and infection are highlighted.
Thangamani
Saravanan
S
Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America. sathanga@utmb.edu
Higgs
Stephen
S
Ziegler
Sarah
S
Vanlandingham
Dana
D
Tesh
Robert
R
Wikel
Stephen
S
D000330:Aedes; D000818:Animals; D002646:Chikungunya virus / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D004199:Disease Vectors; D005260:Female; D007109:Immunity; D007267:Injections; D051379:Mice; D009339:Needles; D012867:Skin / Q000276:immunology / Q000821:virology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology
D016207:Cytokines