Abstract
Simple SummaryParatuberculosis (PTB) is a chronic debilitating disease caused by Mycobacterium avium subspecies paratuberculosis (Map) that affects ruminants worldwide. Many aspects related to the pathogenesis of this disease are still unknown, including the inflammatory acute-phase response developed during the course of the infection. To clarify this, serum levels of haptoglobin and serum amyloid A, two positive acute-phase proteins, were evaluated in a total of 190 cows, among which 59 were healthy control animals and 131 cows were diagnosed post-mortem with different types of lesion associated with Map-infection. The results reflect a significant increase of these proteins’ levels in the infected animals and, more specifically, in those animals with types of lesion characterized by a low bacterial load and with predominance of a cell-mediated immune response. This suggests that these molecules would play a certain role in the pathogenesis of the PTB and a possible utility as biomarkers of different stages of the disease.In this study, the concentrations of two acute-phase proteins (APPs), haptoglobin (Hp) and serum amyloid A (SAA), were quantitatively assessed in serum samples from cattle naturally infected with paratuberculosis (PTB). APP profiles were compared across 190 animals classified according to the different pathological forms associated with infection: uninfected (n = 59), with focal lesions (n = 73), multifocal lesions (n = 19), and diffuse paucibacillary (n = 11) and diffuse multibacillary lesions (n = 28). Our results showed a significant increase in both APPs in infected animals compared to the control group, with differences depending on the type of lesion. Hp and SAA levels were increased significantly in all infected animals, except in cows with diffuse multibacillary lesions that showed similar values to non-infected animals. The expression pattern of both APPs was similar and negatively correlated with the antibody levels against PTB. These results indicate that the release of Hp and SAA is related to the presence of PTB lesions associated with a high cell-mediated immune response and a lower bacterial load, suggesting that the pro-inflammatory cytokines that are associated with these forms are the main stimulus for their synthesis. These molecules could show some potential to be used as putative biomarkers of PTB infection, particularly for the identification of subclinical animals showing pathological forms related to latency or resistance to the development of advanced lesions.
Highlights
Paratuberculosis (PTB) is a chronic debilitating disease characterized by a granulomatous enteritis and lymphadenitis that affects ruminants worldwide, caused by the facultative intracellular pathogenMycobacterium avium subspecies paratuberculosis (Map) and responsible for high economic losses to domestic livestock [1]
A certain number of these chronically infected animals can gradually develop clinical signs that are associated with a diffuse granulomatous enteritis, which widely affects several areas of the intestine with variations according to the main inflammatory cells present in the infiltrate and the amount of Map, so that two main forms are recognized: multibacillary and paucibacillary forms [5,6].The development of these different lesions is closely related to the immune response mounted by the host in each phase of the infection [7,8]
To the best of our knowledge, there is a brief mention of the acute-phase response assessment in Map-infected sheep in a previous study [23], this is the first report that deeply analyzes the Hp and serum amyloid A (SAA) serum values in cows infected with Map in relation to the different pathological forms associated with the disease, both from histological and serological perspectives
Summary
Paratuberculosis (PTB) is a chronic debilitating disease characterized by a granulomatous enteritis and lymphadenitis that affects ruminants worldwide, caused by the facultative intracellular pathogenMycobacterium avium subspecies paratuberculosis (Map) and responsible for high economic losses to domestic livestock [1]. Some animals are resistant to infection [2,3], while others, when they fail to clear the initial infection, may show resilience to disease [4] and remain in a subclinical or asymptomatic stage for a long period of time, even their entire life, in which infection is controlled. In this sense, the formation of granulomas at the site of Map infection is critical. A certain number of these chronically infected animals can gradually develop clinical signs that are associated with a diffuse granulomatous enteritis, which widely affects several areas of the intestine with variations according to the main inflammatory cells present in the infiltrate and the amount of Map, so that two main forms are recognized: multibacillary and paucibacillary forms [5,6].The development of these different lesions is closely related to the immune response mounted by the host in each phase of the infection [7,8]
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