Role of ErbB and IL-1 signaling pathways in the dermonecrotic lesion induced by Loxosceles sphingomyelinases D.

Sphingomyelinase D (SMase D), the main toxic component of Loxosceles venom, has a well-documented role on dermonecrotic lesion triggered by envenomation with these species; however, the intracellular mechanisms involved in this event are still poorly known. Through differential transcriptomics of human keratinocytes treated with L. laeta or L. intermedia SMases D, we identified 323 DEGs, common to both treatments, as well as upregulation of molecules involved in the IL-1 and ErbB signaling. Since these pathways are related to inflammation and wound healing, respectively, we investigated the relative expression of some molecules related to these pathways by RT-qPCR and observed different expression profiles over time. Although, after 24 h of treatment, both SMases D induced similar modulation of these pathways in keratinocytes, L. intermedia SMase D induced earlier modulation compared to L. laeta SMase D treatment. Positive expression correlations of the molecules involved in the IL-1 signaling were also observed after SMases D treatment, confirming their inflammatory action. In addition, we detected higher relative expression of the inhibitor of the ErbB signaling pathway, ERRFI1, and positive correlations between this molecule and pro-inflammatory mediators after SMases D treatment. Thus, herein, we describe the cell pathways related to the exacerbation of inflammation and to the failure of the wound healing, highlighting the contribution of the IL-1 signaling pathway and the ERRFI1 for the development of cutaneous loxoscelism.

Immune-related redox metabolism of embryonic cells of the tick Rhipicephalus microplus (BME26) in response to infection with Anaplasma marginale.

BACKGROUND: It is well known that reactive oxygen species (ROS) and reactive nitrogen species (RNS) are involved in the control of pathogens and microbiota in insects. However, the knowledge of the role of ROS and RNS in tick-pathogen and tick-microbiota interactions is limited. Here, we evaluated the immune-related redox metabolism of the embryonic cell line BME26 from the cattle tick Rhipicephalus microplus in response to Anaplasma marginale infection. METHODS: A high-throughput qPCR approach was used to determine the expression profile of 16 genes encoding proteins involved in either production or detoxification of ROS and RNS in response to different microbial challenges. In addition, the effect of RNAi-mediated gene silencing of catalase, glutathione peroxidase, thioredoxin and protein oxidation resistance 1 in the control of infection with A. marginale was evaluated. RESULTS: Infection with A. marginale resulted in downregulation of the genes encoding ROS-generating enzymes dual oxidase and endoplasmic reticulum oxidase. In contrast, the genes encoding the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase, thioredoxin, thioredoxin reductase and peroxiredoxin were upregulated. The gene expression pattern in response to infection with Rickettsia rickettsii and exposure to heat-killed microorganisms, Micrococcus luteus, Enterobacter cloacae or S. cerevisiae was the opposite of that triggered by A. marginale challenge. The simultaneous silencing of three genes, catalase, glutathione peroxidase, and thioredoxin as well as the oxidation resistance 1 gene by RNAi apparently favoured the colonization of BME26 cells by A. marginale, suggesting that the antioxidant response might play a role in the control of infection. CONCLUSIONS: Taken together, our results suggest that a general response of tick cells upon microbial stimuli is to increase ROS/RNS production. In contrast, A. marginale infection triggers an opposite profile, suggesting that this pathogen might manipulate the tick redox metabolism to evade the deleterious effect of the oxidant-based innate immune response.

New approaches toward anti-Rhipicephalus (Boophilus) microplus tick vaccine.

The tick Rhipicephalus (Boophilus) microplus (formerly Boophilus microplus) is the major ectoparasite affecting livestock in America, Asia, Africa, and Oceania. Conventional tick control is based on the use of acaricides but immunization of bovines with tick gut proteins induces only a partial protective immune response. Based on this information, distinct research groups have explored the possibility of protecting the animals by inducing an immune response against other tick proteins. However, the antigens so far described do not induce the necessary protection for suppressing the use of acaricides. Currently, several groups are engaged in identifying new tick proteins to be used as targets for the development of new vaccines. This approach focuses on the enhancement of the immunogenicity of antigens already tested by incorporating new adjuvants or formulations and by searching for new antigens. This paper reviews the work done by Brazilian researchers to develop a vaccine against this tick.

New approaches toward anti-Rhipicephalus (Boophilus) microplus tick vaccine / Novas estratégias para o desenvolvimento de uma vacina contra o carrapato Rhipicephalus (Boophilus) microplus

The tick Rhipicephalus (Boophilus) microplus (formerly Boophilus microplus) is the major ectoparasite affecting livestock in America, Asia, Africa, and Oceania. Conventional tick control is based on the use of acaricides but immunization of bovines with tick gut proteins induces only a partial protective immune response. Based on this information, distinct research groups have explored the possibility of protecting the animals by inducing an immune response against other tick proteins. However, the antigens so far described do not induce the necessary protection for suppressing the use of acaricides. Currently, several groups are engaged in identifying new tick proteins to be used as targets for the development of new vaccines. This approach focuses on the enhancement of the immunogenicity of antigens already tested by incorporating new adjuvants or formulations and by searching for new antigens. This paper reviews the work done by Brazilian researchers to develop a vaccine against this tick.

O carrapato Rhipicephalus (Boophilus) microplus (anteriormente Boophilus microplus) é o principal ectoparasita que afeta bovinos na América, Ásia, África e Oceania e o seu controle é tradicionalmente realizado através do uso de acaricidas. Experimentos de imunização com proteínas do carrapato mostram que a resposta imune desenvolvida pelos bovinos vacinados protege, em parte, os animais do parasitismo. Baseado nessas observações, vários grupos de pesquisa exploram a possibilidade de proteger os animais pela indução de uma resposta imune contra proteínas do carrapato. Entretanto, os antígenos já caracterizados não asseguram o grau de proteção necessário para suprimir o uso de acaricidas. Portanto, esses grupos de pesquisa estão engajados na tentativa de identificar novas proteínas que possam ser utilizadas para o desenvolvimento de novas vacinas, as quais possam induzir maior imunogenicidade de que os antígenos já testados, através do uso de novas formulações e/ou pela incorporação de adjuvantes. O presente artigo apresenta uma revisão da literatura sobre os resultados obtidos por pesquisadores brasileiros no desenvolvimento de vacinas contra o carrapato.