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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Molecular Innate Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1463471
This article is part of the Research Topic Community Series in the Role of Complement in Health and Disease: Volume II View all 8 articles

Africanized honeybee venom (Apis mellifera) promotes human complement activation split products storm

Provisionally accepted
Felipe Silva de França Felipe Silva de França 1,2Ricardo De Oliveira Orsi Ricardo De Oliveira Orsi 3Dayanne C. Fernandes Dayanne C. Fernandes 1,2Thyago B. Leonel Thyago B. Leonel 1,2Denise V. Tambourgi Denise V. Tambourgi 1,2*
  • 1 Laboratory of Immunochemistry, Butantan Institute, São Paulo, Brazil
  • 2 Center of Toxins, Cell Signaling and Immune Response (CeTICS) – CEPID - FAPESP, São Paulo, Brazil
  • 3 Center of Education, Science and Technology in Rational Beekeeping (NECTAR), College of Veterinary Medicine and Animal Sciences, São Paulo State University, Botucatu, São Paulo, Brazil., Botucatu, Brazil

The final, formatted version of the article will be published soon.

    Complement activation split products are signatures of many immunopathological disorders. Among the laboratory findings observed in these diseases, a reduction in the level of circulating intact complement components can be mentioned, and this change has also been detected in envenomation by multiple Africanized honeybee (Apis mellifera) stings. Although envenomation by these animals elicits diverse life-threatening reactions, the capacity of bee venom (AmV) to activate the human complement system remains elusive. By coupling immunochemical and functional approaches, it was observed that AmV strongly consumes components of the alternative pathway (AP) of the complement system in normal human serum (NHS). Additionally, AmV interfered with classical (CP) and lectin pathways (LP) activities. In parallel, a high increase in Ba fragment levels was detected, suggesting that the changes in AP activity were due to its activation. Furthermore, an increase in the level of the C1s-C1INH complex and a decrease in the physiological level of MASP1-C1INH suggested that CP and LP were also activated in the presence of AmV. Strikingly, NHS exposed to increasing AmV concentrations varying from 5 to 1000 µg/mL presented a high generation of C3a, C4a and C5a anaphylatoxins, and sC5b-9 complexes assembly, thus reinforcing that AmV triggers complement activation. These results show that AmV is a strong complement activator. This activation presents a mixed profile, with a predominance of AP activation. This suggests that complement split products can play important roles in the envenomation by Africanized honeybee, as they could induce diverse immunopathological events observed in patients and may also dictate patient clinical prognosis.

    Keywords: Complement pathways activation, Anaphylatoxins, Africanized honeybee, Apis mellifera venom, immunopathology

    Received: 12 Jul 2024; Accepted: 14 Oct 2024.

    Copyright: © 2024 Silva de França, De Oliveira Orsi, Fernandes, Leonel and Tambourgi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Denise V. Tambourgi, Laboratory of Immunochemistry, Butantan Institute, São Paulo, Brazil

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