The within host dynamics of Mycobacterium avium ssp. paratuberculosis infection in cattle: where time and place matter

Abstract

Johne’s disease or paratuberculosis, caused by Mycobacterium avium subsp. paratuberculosis (MAP), occurs in domestic and wild animals worldwide, causing a significant economic loss to livestock industries. After a prolonged incubation time, infected cattle shed MAP bacilli into feces and spread the disease to an uninfected animal population. It is largely unknown how (or whether) the interplay between the pathogen and the host immunity determines timing of shedding after the long incubation time. Such information would provide an understanding of pathogenesis in individual animals and the epidemiology of MAP infection in animal populations. In this review, we summarize current knowledge of bovine Johne’s disease pathology, pathogenesis, immunology and genetics. We discuss knowledge gaps that direly need to be addressed to provide a science-based approach to diagnostics and (immuno)prophylaxis. These knowledge gaps are related to anatomical/clinical manifestation of MAP invasion, interaction of bacteria with phagocytes, granuloma formation, shedding, establishment and kinetics of adaptive immune responses in the pathogenesis of the disease. These topics are discussed at the molecular, cellular and tissue levels with special attention to the within host dynamics including the temporal and the spatial context relevant for the various host-pathogen interactions.

Prevalence and Pathology of Paratuberculosis in Cattle and Buffaloes at Faisalabad Abattoir

“…A histopathological study in Indian buffalo revealed inflammation of lymph node and intestine, thickening and corrugation of small intestine and granulomatous inflammation (Sivakumar et al, 2006). A study conducted by Koets et al (2015) revealed that thickening and corrugation of intestine along with enlargement of mesenteric and lymph nodes were prominent in diseased animals. This corrugation and thickening of mucosa may be due to infiltration of mononuclear cells, i.e., epithelioid macrophages infiltration in mucosa and in submucosa (Maxie et al, 2007).…”

“…The pathogenesis of the disease is poorly known. The organism is usually assumed to pass through the lumen of the small intestine and move towards the Peyer's patches via Microfoldcells (M cells) of the follicle associated epithelium, soon this is phagocytized by macrophages (Koets et al, 2015). MAP has ability to survive and replicate within macrophages in the intestine and in the lymph nodes.…”

“…MAP has ability to survive and replicate within macrophages in the intestine and in the lymph nodes. This association of M cell and peyer's patches indicate that the follicle associated epithelium has concern with the uptake of the organism (Koets et al, 2015). The macrophages engulf these bacteria and gradually lead to severe granulomatous inflammation in small and large intestine and in associated mesenteric lymph nodes.…”

Molecular and histopathological evaluation of the efficacy of Saponified and Freund’s incomplete adjuvanted paratuberculosis killed vaccine in murine model

“…paratuberculosis (MAP), which results in serious economic losses worldwide in farmed livestock such as cattle, sheep, and goats (Bannantine et al, 2014). It is characterized by chronic enteritis, progressive debilitation and poor response to therapy with a long subclinical phase, during which shedding of bacteria in faeces may be present (Sweeney et al, 2012;Koets et al, 2015). It is caused by Mycobacterium avium subspecies paratuberculosis (MAP) that has also been suspected for causing regional ileitis or Crohn's disease (CD) in humans (McNees et al, 2015).…”

Within- and between-host mathematical modeling of Mycobacterium avium subspecies paratuberculosis (MAP) infections as a tool to study the dynamics of host-pathogen interactions in bovine paratuberculosis

“…In the opening article Koets et al [1] review the immunobiology of bovine paratuberculosis. The in vivo pathogenesis studies have been largely based on data obtained from cross-sectional studies, mainly with a primary diagnostic focus.…”