High-resolution proteomics unveils salivary gland disruption and saliva-hemolymph protein exchange in Plasmodium-infected mosquitoes
Plasmodium sporozoites, the infective stage of malaria, must invade the mosquito salivary glands (SGs) before being transmitted to a vertebrate host. However, the physiological and biochemical effects of this invasion remain largely unexplored. We examined the impact of Plasmodium infection on Anopheles gambiae salivary glands using high-resolution proteomics, gene expression, and morphological analysis. The data reveal differential expression of various proteins, including the enrichment of hemolymph-derived humoral proteins in infected salivary glands. These proteins diffuse into the SGs due to structural damage caused by the sporozoites during invasion, while saliva proteins diffuse out into the circulation. Moreover, proteomic analysis of saliva from P. berghei- or P. falciparum-infected mosquitoes revealed changes in composition, with a pronounced reduction of immune proteins relative to uninfected mosquitoes. This reduction is likely due to the association of these proteins with the surface of sporozoites and/or changes in the saliva's physical properties within the invaded salivary secretory cavities. The saliva protein profiles from mosquitoes infected with both Plasmodium species are remarkably similar, suggesting a conserved interaction between sporozoites and salivary glands. Our results provide a foundation for understanding the molecular interactions between Plasmodium sporozoites and mosquito salivary glands.
Authors
- Sabrina Absalon (ORCID: https://orcid.org/0000-0003-2468-8156)
- Derron A. Alves
- Janet J. Olivas (ORCID: https://orcid.org/0000-0002-5855-0692)
- Ming Zhao (ORCID: https://orcid.org/0000-0002-5700-2950)
- Carolina Barillas‐Mury (ORCID: https://orcid.org/0000-0002-4039-6199)
- José M. C. Ribeiro (ORCID: https://orcid.org/0000-0002-9107-0818)
- Tales Vicari Pascini (ORCID: https://orcid.org/0000-0001-8759-0362)
- Joel Vega-Rodríguez (ORCID: https://orcid.org/0000-0002-9576-0058)
- Cindi L. Schwartz (ORCID: https://orcid.org/0000-0002-0490-6040)
- Friedrich Frischknecht (ORCID: https://orcid.org/0000-0002-8332-6668)
- Octávio A. C. Talyuli (ORCID: https://orcid.org/0000-0002-7026-463X)
- Sachie Kanatani (ORCID: https://orcid.org/0000-0002-7072-0447)
- Isabelle Coppens (ORCID: https://orcid.org/0000-0001-5549-2362)
- Benjamin Liffner (ORCID: https://orcid.org/0000-0002-1573-6139)
- Thiago Luiz Alves e Silva (ORCID: https://orcid.org/0000-0002-8520-5405)
- Zarna Rajeshkumar Pala (ORCID: https://orcid.org/0000-0003-1201-1551)
- Photini Sinnis (ORCID: https://orcid.org/0000-0003-2954-7547)
- Bianca M. Nagata (ORCID: https://orcid.org/0000-0002-7479-0012)
- Lilian P. Dorner (ORCID: https://orcid.org/0000-0002-8120-7155)
- Ana Beatriz F. Barletta (ORCID: https://orcid.org/0000-0001-9913-3775)
- Motoshi Suzuki (ORCID: https://orcid.org/0000-0002-4346-7677)
Institutions
- National Institutes of Health (US)
- Johns Hopkins University (US)
- Heidelberg University (DE)
- University Hospital Heidelberg (DE)
- German Center for Infection Research (DE)
- National Institute of Allergy and Infectious Diseases (US)
- Indiana University School of Medicine
- Indiana University – Purdue University Indianapolis (US)
- The University of Adelaide (AU)
- New York University (US)
- University of Maryland, College Park (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-11-20
- DOI
- https://doi.org/10.1038/s41467-025-64837-6
- Primary Topic
- Invertebrate Immune Response Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00