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Expression of NRAMP1 and iNOS in Mycobacterium avium subsp. paratuberculosis naturally infected cattle
F Delgado1, C Estrada-Chávez, M Romano
1Instituto Nacional de Tecnología Agropecuaria, Centro Nacional de Investigaciones en Ciencias Veterinarias y Agronómicas, Los Reseros y Las Cabañas, AP CC 77 (1708), Buenos Aires, Argentina.
Abstract:
Paratuberculosis (PTB) is a chronic disease caused by M. avium subsp. paratuberculosis (MAP) that affects several animal species, and some studies have suggested that there may be a relationship between Crohn's disease and PTB. Significant aspects of PTB pathogenesis are not yet completely understood, such as the role of macrophages. Natural resistance-associated macrophage protein 1 (NRAMP1) and the inducible nitric oxide synthase (iNOS) molecules have shown nonspecific effects against several intracellular pathogens residing within macrophages. However, these molecules have been scarcely studied during natural infection with MAP. In this work, changes in NRAMP1 and iNOS expression were surveyed by immunohistochemistry in tissue samples from MAP-infected cattle and healthy controls. Our findings show strong specific immunolabeling against both NRAMP1 and iNOS molecules, throughout granulomatous PTB-compatible lesions in ileum and ileocaecal lymph nodes from paratuberculous cattle compared with uninfected controls, suggesting a relationship between the expression of these molecules and the pathogenesis of PTB disease.
Insights
Paratuberculosis (PTB) involves Mycobacterium avium subsp. paratuberculosis (MAP). This study investigated macrophage proteins NRAMP1 and iNOS in MAP-infected cattle, finding their expression linked to disease pathogenesis.
Area of Science:
- Veterinary Pathology
- Immunology
- Microbiology
Background:
- Paratuberculosis (PTB) is a chronic intestinal disease in ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP).
- The precise role of macrophages in PTB pathogenesis remains incompletely understood.
- Natural resistance-associated macrophage protein 1 (NRAMP1) and inducible nitric oxide synthase (iNOS) are key macrophage molecules involved in combating intracellular pathogens but are understudied in natural MAP infections.
Purpose of the Study:
- To investigate the expression patterns of NRAMP1 and iNOS in the context of natural MAP infection in cattle.
- To determine if NRAMP1 and iNOS expression correlates with the development of PTB-compatible lesions.
Main Methods:
- Immunohistochemistry was employed to analyze tissue samples from MAP-infected cattle and healthy controls.
- Specific immunolabeling was used to quantify the expression levels of NRAMP1 and iNOS.
- Tissues examined included the ileum and ileocaecal lymph nodes.
Main Results:
- Strong and specific immunolabeling for both NRAMP1 and iNOS was observed in granulomatous lesions characteristic of PTB.
- These findings were evident in the ileum and ileocaecal lymph nodes of paratuberculous cattle.
- Expression levels were significantly higher in infected animals compared to uninfected controls.
Conclusions:
- The study suggests a significant association between the expression of NRAMP1 and iNOS and the pathogenesis of paratuberculosis in cattle.
- These macrophage-associated molecules may play a crucial role in the host's response to MAP infection.
- Further research into these molecules could elucidate PTB disease mechanisms and potential therapeutic targets.
