Expression of transforming growth factor-beta 1 (TGF-β1) in different types of granulomatous lesions in bovine and ovine paratuberculosis

Macrophage Subsets Within Granulomatous Intestinal Lesions in Bovine Paratuberculosis

“…Thus, although there is a reduced Map multiplication and low numbers of new macrophages recruited from the blood, the increased expression of TGF-b could indicate that they are starting to progress to more severe and uncontrolled lesions. 27,36 CD68 and lysozyme have been widely used as general macrophage markers, 2,29,43,46,55 which is in agreement with our findings, since they have been found in all the lesion types. However, their expression is shown to be positively correlated with the number of AFB, with the highest H-score levels observed in diffuse multibacillary lesions, as previously reported in paratuberculosis.…”

“…27,35 This scenario is consistent with the low levels of iNOS and TNF-a (a well-known proinflammatory cytokine) expression found in this type of lesions opposed to those found in focal forms. In paratuberculosis infection, upregulation of TGF-b and IL-10 has been reported in clinical cases during the late stages of the disease, 1,27 which are highly expressed in macrophages harboring high numbers of Map, 36,53 in agreement with our results. Expression of MHC class II was significantly higher in diffuse multibacillary lesions compared to the rest of the lesion types.…”

Histopathological Characterization of Cutaneous Delayed-type Hypersensitivity and Correlations with Intestinal Pathology and Systemic Immune Responses in Sheep with Paratuberculosis

“…The perivascular infiltration of lymphocytes observed in this study is a consistent feature in mycobacterial skin sensitization (Poulter and Lefford, 1977;Samuel et al, 1985;Narayanan et al, 1986;Beck et al, 1988;Kaplan et al, 1988). Periadnexal infiltrates have been reported in the cutaneous DTH reaction in people with tuberculosis (Haholu et al, 2008) and in healthy sheep sensitized by Mycobacterium bovis vaccination (Pyrah and Watt, 1995).…”

“…IL-10-producing regulatory T cells have been suggested to be involved in immune regulation of host responses leading to MAP survival (Coussens et al, 2012) and systemic IL-10 responses were increased in sheep with multibacillary disease (de Silva et al, 2010). Immune regulatory molecules, including IL-10, transforming growth factor-b and indoleamine 2, 3-dioxygenase, have been shown to be preferentially expressed within lesions of animals with late-stage disease, consistent with a role for immunosuppression leading to the reduced capacity to limit the proliferation of MAP in these animals (Khalifeh and Stabel, 2004;Munoz et al, 2009;Plain et al, 2011). It is unclear how dissemination of MAP to peripheral sites is related to changes in immune function; this could be a causal mechanism in the immune dysfunction or the result of reduced immune surveillance.…”

“…The skin test for tuberculosis, first discovered by Robert Koch in 1882 (Black, 1999), is measured as a change in skin fold thickness or induration 48e72 h following intradermal injection of mycobacterial antigen, compared against diagnostic criteria to determine a positive or negative result. While the cutaneous DTH reaction to mycobacterial antigen has been well described in other species such as man and mice (Baumgarten and Wilhelm, 1969;Poulter and Lefford, 1977;Samuel et al, 1985;Narayanan et al, 1986;Beck et al, 1988;Kaplan et al, 1988;Black, 1999;Vukmanovic-Stejic et al, 2006;Haholu et al, 2008), it has not been described in MAP-affected sheep beyond the association of gut pathology with measurement of induration. High induration was associated with paucibacillary gut lesions, while no change in skin thickness or low levels of induration were associated with multibacillary gut lesions (Gilmour and Brotherston, 1966;Gilmour et al, 1978;Perez et al, 1999).…”