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Biomedical subjects

Louis C Gasbarre

Publications and source records attributed to Louis C Gasbarre.

5 recordsLinked to original sources

Local inflammation as a possible mechanism of resistance to gastrointestinal nematodes in Angus heifers.

Understanding mechanisms of resistance to gastrointestinal nematodes is important in developing effective and sustainable control programs. A resource population of Angus cattle consisting of approximately 600 animals with complete pedigree records has been developed. The majority of these animals were completely characterized for their resistance to natural challenge by gastrointestinal nematodes. As the first step towards understanding the molecular basis of disease resistance, we investigated expression profiles of 17 cytokines, cytokine receptors, and chemokines using real-time RT-PCR in animals demonstrating resistance or susceptibility to pasture challenge. The animals exposed to natural infection for approximately 6 months were treated to remove existing parasites and then experimentally challenged with both Ostertagia ostertagi and Cooperia oncophora. The mRNA expression profiles of these genes in abomasal and mesenteric lymph nodes (ALN, MLN), fundic and pyloric abomasa (FA, PA), and small intestine (SI) were compared between resistant and susceptible animals. Resistant heifers exhibited elevated expression of inflammatory cytokines such as TNFalpha, IL-1beta, and MIP-1alpha in fundic and pyloric abomasa 7 days post infection. Expression levels of IL-10, polymeric immunoglobullin receptor gene (PIGR), and WSX-1 were also 2.7-19.9-folds higher in resistant than susceptible heifers in these tissues. No difference in expression of CXCL6, CXCL10, IFN-gamma, IL-2, IL-4, IL-6, IL-8, IL-12 p40, IL-13, IL-15 and IL-18 was observed between the two groups. The expression of MIP-1alpha, IL-6, and IL-10 was also elevated in small intestines in resistant animals. In contrast, little difference in expression of these genes was detected between resistant and susceptible groups in the draining lymph nodes. These data indicate that resistant animals can better maintain inflammatory responses at the site of infection, suggesting a possible novel mechanism of resistance.

Animals↗

Discovery and profiling of bovine microRNAs from immune-related and embryonic tissues.

MicroRNAs are small approximately 22 nucleotide-long noncoding RNAs capable of controlling gene expression by inhibiting translation. Alignment of human microRNA stem-loop sequences (mir) against a recent draft sequence assembly of the bovine genome resulted in identification of 334 predicted bovine mir. We sequenced five tissue-specific cDNA libraries derived from the small RNA fractions of bovine embryo, thymus, small intestine, and lymph node to validate these predictions and identify new mir. This strategy combined with comparative sequence analysis identified 129 sequences that corresponded to mature microRNAs (miR). A total of 107 sequences aligned to known human mir, and 100 of these matched expressed miR. The other seven sequences represented novel miR expressed from the complementary strand of previously characterized human mir. The 22 sequences without matches displayed characteristic mir secondary structures when folded in silico, and 10 of these retained sequence conservation with other vertebrate species. Expression analysis based on sequence identity counts revealed that some miR were preferentially expressed in certain tissues, while bta-miR-26a and bta-miR-103 were prevalent in all tissues examined. These results support the premise that species differences in regulation of gene expression by miR occur primarily at the level of expression and processing.

Animals↗

Recombinant bovine interleukin-12 stimulates a gut immune response but does not provide resistance to Cryptosporidium parvum infection in neonatal calves.

This study was undertaken to determine if administration of recombinant bovine interleukin-12 (rBoIL-12) could stimulate a cellular immune response that protected calves from an oral challenge inoculation with Cryptosporidium parvum oocysts. In a first experiment, rBoIL-12 intraperitoneally administered as a single dose 1 day before challenge inoculation, did not alter the course of infection. The percentage of immune competent cells and levels of cytokine gene expression in the ileo-cecal mucosa and in the draining lymph nodes of treated calves were similar to those of untreated control calves. However, when rBoIL-12 was subcutaneously administered daily from 2 days before infection to 2 days after infection, a consistent increase of T lymphocytes and an higher expression of interferon-gamma (IFN-gamma) was detected. Again, treatment did not alter the course of infection. Similar results were obtained when rBoIL-12 was administered daily for 4 days beginning 2 days after oral inoculation. These data indicate that although rBoIL-12 stimulated a strong immune response in the gut of neonatal calves, the response was not able to provide protection from challenge inoculation with C. parvum oocysts.

Animals↗

Gastrointestinal nematode control programs with an emphasis on cattle.

Control strategies for nematode parasites rely on knowledge of the relationships between the parasites and their hosts. Specifically, these programs are based on identifying crucial points of interaction in the environment provided by the host, including genetics and the immune response, and critical periods in the physical environment in which the eggs and larval stages must develop. When these targets are identified and the interactions understood, cost-effective sustainable programs can be developed using currently available antiparasitic compounds. Resistance to the major classes of anthelmintic compounds requires consideration of new approaches, such as immunity or genetics of the host. Additionally, the efficacy of these compounds can be expanded with combined or concomitant use. Increased study of the use of novel approaches, including fungi, elements such as copper, and plant products, has also occurred. This article explores each of these areas to allow readers to appreciate how various approaches may be developed and incorporated into an effective parasite control program.

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