Host Inflammatory Response to Mosquito Bites Enhances the Severity of Arbovirus Infection

Marieke Pingen, et al., 2016, Immunity 44, 1455–1469

Speaker: Irwin Puc (傅立宇)                                                 Time: 15:00-16:00, Nov. 1, 2017

Commentator: Dr. Yee-Shin Lin (林以行)                          Place: Room 601

Abstract:

The immune response plays a crucial role in our body, this is how our body recognizes and defends itself against bacteria, viruses and substances that appears foreign or harmful to the body. During the earliest stages of a virus infection, the production of cytokines initiates as soon as the innate immune defenses are activated. This rapid release of cytokines at the site of infection initiates new cascading responses far-reaching consequences that includes inflammation, heat, swelling, and pain, which are a consequence of increased blood flow and capillary permeability, the influx of phagocytic cells, and tissue damage. The skin is the first line of defense against any pathogen, all mosquito-borne viruses share a common attribute which is their site of inoculation at mosquito bite sites. Many published journals have shown that saliva from biting mosquitos have a potent effect on various mammalian biological processes which aids in enhancing subsequent disease severity. It has been hypothesized that, due to the importance of type 1 interferons (IFNs) and T cell responses in antiviral immunity, their function is perturbed by the mosquito saliva. In this paper the author shows that rather than perturbing anti-viral immune responses, mosquito bites trigger a leukocyte influx that facilitates infection by providing new cellular targets for infection.  Neutrophils are one of the earliest types of phagocytic cells that enter a site of infection, and are classic markers of the inflammatory response, in this journal a two-step process was identified, in which mosquito bites caused an influx of inflammatory neutrophils that helped coordinate innate immune responses and pave the way for the chemokine receptor CCR2-dependent entry of myeloid cells that are permissive to viral infection. Furthermore, mosquito bites evoked a pronounced edema that retained more of the virus inoculum in the skin and facilitated infection of these cutaneous cells. Unprecedented data showed that, Inhibition of key components of the inflammatory response to the bite reduced leukocyte influx, suppressed viral replication, and increased host survival. These findings not only define the mosquito bite site as a putative target for post-exposure prophylactic intervention, but also this crucial aspect of their life cycle is a bottleneck that can limit dissemination of virus to the bloodstream, the development of clinically apparent disease and might provide a novel target for preventing diseases spread by this vector.

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