Biomedical subjects

Jeremy F Fuchs

Publications and source records attributed to Jeremy F Fuchs.

3 recordsLinked to original sources

PubMed2005

Mosquito innate immunity: involvement of beta 1,3-glucan recognition protein in melanotic encapsulation immune responses in Armigeres subalbatus.

Beta 1,3-glucan recognition proteins (GRP) have specific affinity for beta 1,3-glucan, a component on the surface of fungi and bacteria. By interacting with beta 1,3-glucan, GRP initiates activation of prophenoloxidase, a key enzyme in the signaling pathway leading to melanotic encapsulation in invertebrates. In this study, we characterize a novel hemocyte-specific GRP from the mosquito, Armigeres subalbatus (AsGRP). The 1.57 kb cDNA clone encodes a 499 deduced amino acid sequence, which contains a region that displays significant similarity to the glucanase-like regions of other GRPs and Gram-negative bacteria binding proteins found in other organisms. AsGRP is constitutively expressed in the hemolymph of adult female mosquitoes, and is upregulated following challenge with Escherichia coli, Micrococcus luteus, and the filarial worm Dirofilaria immitis. AsGRP specifically recognizes curdlan (insoluble beta 1,3-glucan), but not mannose or N-acetyl-D-glucosamine. AsGRP binds a low percentage of E. coli, most M. luteus and D. immitis microfilariae. AsGRP double-stranded RNA interference strongly inhibits melanotic encapsulation of D. immitis in Ar. subalbatus. These results suggest that AsGRP has the capacity to bind to a variety of pathogens, functions as a pattern recognition receptor, and is required for effective melanotic encapsulation immune responses in Ar. subalbatus.

Acetylglucosamine↗

PubMed2005

Age-associated mortality in immune challenged mosquitoes (Aedes aegypti) correlates with a decrease in haemocyte numbers.

Mosquitoes vector pathogens. One aspect that has been overlooked in mosquito-pathogen relationships is the effect of host age on immune competence. Here, we show that there is age-associated mortality following immune challenge with Escherichia coli. This mortality correlates with a decrease in haemocyte numbers (blood cells) and a decreased ability to kill E. coli. Although the number of haemocytes decreases, the available haemocytes retain their phagocytic ability regardless of age, and we estimate that individual granulocytes can phagocytose approximately 1500 E. coli. Moreover, transcription profiles for cecropin, defensin and gambicin in E. coli challenged mosquitoes do not change with age, indicating that the increased susceptibility is not attributed to fewer humoral antimicrobial peptides. These results suggest that a contributing factor for the age-associated mortality is the decrease in circulating haemocytes, which reduces the overall phagocytic capacity of mosquitoes. To our knowledge, this is the first report detailing an age-associated decline in the immunological capabilities of mosquitoes following challenge with an infectious agent. These data also call for caution in the analysis and interpretation of experimental results when mosquito age has not been closely monitored. Lastly, a model for haemocyte function is presented.

Aging↗

PubMed2004

Description of the transcriptomes of immune response-activated hemocytes from the mosquito vectors Aedes aegypti and Armigeres subalbatus.

Mosquito-borne diseases, including dengue, malaria, and lymphatic filariasis, exact a devastating toll on global health and economics, killing or debilitating millions every year (54). Mosquito innate immune responses are at the forefront of concerted research efforts aimed at defining potential target genes that could be manipulated to engineer pathogen resistance in vector populations. We aimed to describe the pivotal role that circulating blood cells (called hemocytes) play in immunity by generating a total of 11,952 Aedes aegypti and 12,790 Armigeres subalbatus expressed sequence tag (EST) sequences from immune response-activated hemocyte libraries. These ESTs collapsed into 2,686 and 2,107 EST clusters, respectively. The clusters were used to adapt the web-based interface for annotating bacterial genomes called A Systematic Annotation Package for Community Analysis of Genomes (ASAP) for analysis of ESTs. Each cluster was categorically characterized and annotated in ASAP based on sequence similarity to five sequence databases. The sequence data and annotations can be viewed in ASAP at https://asap.ahabs.wisc.edu/annotation/php/ASAP1.htm. The data presented here represent the results of the first high-throughput in vivo analysis of the transcriptome of immunocytes from an invertebrate. Among the sequences are those for numerous immunity-related genes, many of which parallel those employed in vertebrate innate immunity, that have never been described for these mosquitoes. The sequences and annotations presented in this paper have been submitted to GenBank under accession numbers AY 431103 to AY 433788 (Aedes aegypti) and AY 439334 to AY 441440 (Armigeres subalbatus).

Aedes↗