|Motoko, Morimoto - YAMAGUCHI UNIV., JAPAN|
Submitted to: Proceedings of Allen D Leman Swine Conference
Publication Type: Proceedings
Publication Acceptance Date: August 20, 2001
Publication Date: August 20, 2001
Citation: Solano Aguilar, G., Beshah, E., Motoko, M., Schoene, N.W., Urban Jr, J.F. 2001. Localized immunity to the large roundworm ascaris suum in swine. Proceedings of Allen D Leman Swine Conference. Interpretive Summary: Pathogens that generally enter the host through mucosal surfaces in the intestine and lung airways can have unique effects on the immune system that regulates responses to infection at these sites. It is known that the nutritional status of the host can affect the level and nature of the immune response to infectious agents. One expression of immunity is an increased oxidative burst by inflammatory cells that is meant to control infection, but often has harmful side effects on host tissue. An infection model was designed in pigs to study the local response to a parasitic infection in the lungs. The pig provides physiological and immunological responses that are more similar to humans than experimental rodent models of infection. Parasitic nematode infections stimulate immune responses that are equivalent to allergic responses and are convenient tools for stimulating local immunity in a way that is similar to expression of asthma and allergy in the lung. The cellular and molecular responses to this infection have been partially characterized to provide baseline information that can be used when the diet of the animal is altered to change its nutritional status which can then be evaluated compared to the predicted response. This system can be useful in examining how nutrients like trace minerals and vitamins can modulate the immune response to an infectious agent that invades the lungs or the response to an allergen. Reducing the level of the response or changing its nature to prevent excess tissue destruction through dietary interventions is the goal of this project. The results will also provide useful markers of immune function and the nature of their response to changes in diet.
Technical Abstract: Ascaris suum induces a strong type 2 immune response. It was hypothesized that migration of larvae through the lungs of pigs could stimulate a local type 2-response and affect cells in the bronchoalveolar lavage (BAL). An earlier study demonstrated reduced phagocytic activity of alveolar macrophages (AM) during an infection. Changes in the cellular composition of the BAL and the function of AM were evaluated at different times after infection with A. suum. The phenotype of cells in the BAL and changes in intracellular tyrosine phosphorylation were measured by flow cytometry at 7, 11, 14, 28, 32 and 35 days after a primary inoculation (pi) with A.suum eggs. A second set of pigs was re-infected on day 21 after initial infection and the BAL evaluated 7, 11 and 14 days pi There is a reduction in the relative numbers of AM in the BAL that corresponds to an increase in the number of eosinophils with time after inoculation. These changes were greatest at 14 days pi when AM made up 98% of BAL in uninfected pigs compared to 44% in infected pigs, while the percentage of eosinophils was 0% and 49% respectively. This change corresponded to an increase in IL-4 and IL-5 gene expression in the lung and draining lymph nodes. A similar response was observed during a secondary inoculation with eggs. The increase in eosinophils in the BAL was associated with altered AM function. The level of tyrosine phosphorylation in AM was assessed using a specific monoclonal antibody that detects phosphorylated-tyrosine residues. A reduction in intracellular tyrosine phosphorylation was most pronounced at 11 days pi. It is postulated that a reduced ability of AM to become activated could compromise both innate and acquired immunity to microbial pathogens at the pulmonary mucosa.