Immunohistochemical expression of TLR1, TLR2, TLR4, and TLR9 in the different types of lesions associated with bovine paratuberculosis.

The factors that determine the appearance of the different pathologic forms associated with bovine paratuberculosis are not fully understood, but new research suggests a critical role of innate immunity. Toll-like receptors (TLRs) trigger the recognition of invading pathogens by innate immune cells and the onset of specific immune responses. The aim of this work was to assess, immunohistochemically, the expression of TLR1, TLR2, TLR4, and TLR9 in intestinal samples of 20 cows showing different types of paratuberculous lesions: uninfected controls, focal lesions, paucibacillary, and multibacillary diffuse forms. The majority of labeled cells were morphologically consistent with macrophages. A differential cell count was performed in the intestinal lamina propria, gut-associated lymphoid tissue, and mesenteric lymph node. TLR9 immunolabeling between the different types of lesions was compared using a complete H-score. Focal and diffuse paucibacillary forms contained significantly increased TLR2-expressing macrophages outside of the lesions compared with the controls and diffuse multibacillary forms, and moderate TLR9 immunolabeling within granulomas. In the multibacillary granulomatous lesions, the expression of TLR1 and TLR4 was observed as well as increased TLR9 expression compared with the rest of the groups. Differences in the predominance of one type or another of TLR allows us to elucidate the importance of the innate immune response and its possible role in the development of the different types of paratuberculosis lesions.