Evaluation of inflammatory skin infiltrate following Aedes aegypti bites in sensitized and non‐sensitized mice reveals saliva‐dependent and immune‐dependent phenotypes

Abstract

Summary During probing and blood feeding, haematophagous mosquitoes inoculate a mixture of salivary molecules into their vertebrate hosts’ skin. In addition to the anti‐haemostatic and immunomodulatory activities, mosquito saliva also triggers acute inflammatory reactions, especially in sensitized hosts. Here, we characterize the oedema and the cellular infiltrate following Aedes aegypti mosquito bites in the skin of sensitized and non‐sensitized BALB/c mice by flow cytometry. Ae. aegypti bites induced an increased oedema in the ears of both non‐sensitized and salivary gland extract‐ (SGE‐)sensitized mice, peaking at 6 hr and 24 hr after exposure, respectively. The quantification of the total cell number in the ears revealed that the cellular recruitment was more robust in SGE‐sensitized mice than in non‐sensitized mice, and the histological evaluation confirmed these findings. The immunophenotyping performed by flow cytometry revealed that mosquito bites were able to produce complex changes in cell populations present in the ears of non‐sensitized and SGE‐sensitized mice. When compared with steady‐state ears, the leucocyte populations significantly recruited to the skin after mosquito bites in non‐sensitized and sensitized mice were eosinophils, neutrophils, monocytes, inflammatory monocytes, mast cells, B‐cells and CD4+ T‐cells, each one with its specific kinetics. The changes in the absolute number of cells suggested two cell recruitment profiles: (i) a saliva‐dependent migration; and (ii) a migration dependent on the immune status of the host. These findings suggest that mosquito bites influence the skin microenvironment by inducing differential cell migration, which is dependent on the degree of host sensitization to salivary molecules.

Disease Resolution in Chikungunya—What Decides the Outcome?

“…of mosquitoes have more robust cellular infiltration than nonsensitized mice. This study suggests that mosquito saliva has the ability to differentially regulate cellular microenvironment around the bite site (55). Another recent study correlated the initial events of mosquito bite and viral inoculation with subsequent development of systemic disease, highlighting an important role for cutaneous innate immune response.…”

Zika Virus Infection of Murine and Human Neutrophils and their Function as Trojan Horses to the Placenta

“…CC-BY-ND 4.0 International license perpetuity. It is made available under a preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in The copyright holder for this this version posted September 16, 2021. ; https://doi.org/10.1101/2021.09.14.460378 doi: bioRxiv preprint recruited to the skin after mosquito bites (46). Thus, we sought to evaluate whether the saliva from the ZIKV vector Aedes aegypti would play a role in facilitating infection in mice.…”

“…Mosquito's saliva is composed of several molecules, including NeSt1 protein (neutrophil-stimulating factor 1) that potently stimulates IL-1β and CCL2 secretion, with further neutrophilic infiltration to the site of infection, promoting viral replication and increasing disease severity (16,46,53). Local immune inflammation recruits myeloid cells, including neutrophils and macrophages, that may act as virus reservoir and carriers to the lymph nodes and other tissues.…”

Papel dos neutrófilos e células T CD8 na infecção por Zika vírus

“…Aedes aegypti infectado [36][37][38] . Sabe-se que a saliva de mosquito vetor é composta por várias moléculas que possuem capacidade de alterar a resposta imune 255 e celularidade local 238 com aumento extraordinário no número de neutrófilos poucas horas após a picada 125,238 . Em nossos resultados de proteômica, foi possível detectar vários membros da família de proteínas Anexina A, porém apenas a A3 foi expressa diferentemente entre os grupos analisados.…”

“…a pele após a picada do mosquito238 . Como o ZIKV é um arbovírus, nós avaliamos se a saliva de mosquito Aedes aegypti poderia facilitar a infecção por…”