Anopheline mosquitoes are the primary vectors of parasites in the genus Plasmodium, the causative agents of malaria. Malaria parasites undergo a series of complex transformations upon ingestion by the mosquito host. During this process, the physical barrier of the midgut epithelium, along with innate immune defenses, functionally restrict parasite development. Although these defenses have been studied for some time, the regulatory factors that control them are poorly understood. The protein kinase C (PKC) gene family consists of serine/threonine kinases that serve as central signaling molecules and regulators of a broad spectrum of cellular processes including epithelial barrier function and immunity. Indeed, PKCs are highly conserved, ranging from 7 isoforms in Drosophila to 16 isoforms in mammals, yet none have been identified in mosquitoes. Despite conservation of the PKC gene family and their potential as targets for transmission-blocking strategies for malaria, no direct connections between PKCs, the mosquito immune response or epithelial barrier integrity are known. Here, we identify and characterize six PKC gene family members--PKCδ, PKCε, PKCζ, PKD, PKN, and an indeterminate conventional PKC--in Anopheles gambiae and Anopheles stephensi. Sequence and phylogenetic analyses of the anopheline PKCs support most subfamily assignments. All six PKCs are expressed in the midgut epithelia of A. gambiae and A. stephensi post-blood feeding, indicating availability for signaling in a tissue that is critical for malaria parasite development. Although inhibition of PKC enzymatic activity decreased NF-κB-regulated anti-microbial peptide expression in mosquito cells in vitro, PKC inhibition had no effect on expression of a panel of immune genes in the midgut epithelium in vivo. PKC inhibition did, however, significantly increase midgut barrier integrity and decrease development of P. falciparum oocysts in A. stephensi, suggesting that PKC-dependent signaling is a negative regulator of epithelial barrier function and a potential new target for transmission-blocking strategies.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795702PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0076535PLOS

Publication Analysis

Top Keywords

epithelial barrier
16
pkc gene
12
gene family
12
protein kinase
8
malaria parasite
8
anopheline mosquitoes
8
midgut epithelium
8
parasite development
8
barrier function
8
transmission-blocking strategies
8

Similar Publications

Introduction: Enterotoxic (ETEC) is the main pathogen that causes diarrhea, especially in young children. This disease can lead to substantial morbidity and mortality and is a major global health concern. Managing ETEC infections is challenging owing to the increasing prevalence of antibiotic resistance.

View Article and Find Full Text PDF

E. Coli cytotoxic necrotizing factor-1 promotes colorectal carcinogenesis by causing oxidative stress, DNA damage and intestinal permeability alteration.

J Exp Clin Cancer Res

January 2025

Department of Cardiovascular, Endocrine-Metabolic Diseases and Aging, Istituto Superiore di Sanità, Rome, Italy.

Background: Bacterial toxins are emerging as promising hallmarks of colorectal cancer (CRC) pathogenesis. In particular, Cytotoxic Necrotizing Factor 1 (CNF1) from E. coli deserves special consideration due to the significantly higher prevalence of this toxin gene in CRC patients with respect to healthy subjects, and to the numerous tumor-promoting effects that have been ascribed to the toxin in vitro.

View Article and Find Full Text PDF

Background: The microbiome regulates the respiratory epithelium's immunomodulatory functions. To explore how the microbiome's biodiversity affects microbe-epithelial interactions, we screened 58 phylogenetically diverse microbes for their transcriptomic effect on human primary bronchial air-liquid interface (ALI) cell cultures.

Results: We found distinct species- and strain-level differences in host innate immunity and epithelial barrier response.

View Article and Find Full Text PDF

SARS-CoV-2 is a viral infection, best studied in the context of epithelial cell infection. Epithelial cells, when infected with SARS-CoV-2 express the viral S-protein, which causes host cells to fuse together into large multi-nucleated cells known as syncytia. Because SARS-CoV-2 infections also frequently present with cardiovascular phenotypes, we sought to understand if S-protein expression would also result in syncytia formation in endothelial cells.

View Article and Find Full Text PDF

Epithelia are multicellular sheets that form barriers defining the internal and external environments. The constant stresses acting at this interface require that epithelial sheets are mechanically robust and provide a selective barrier to the hostile exterior. These properties are mediated by cellular junctions which are physically linked with heavily crosslinked cytoskeletal networks.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!