A murine oral model for Mycobacterium avium subsp. paratuberculosis infection and immunomodulation with Lactobacillus casei ATCC 334

Abstract

Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis) the causative agent of Johne's disease, is one of the most serious infectious diseases in dairy cattle worldwide. Due to the chronic nature of this disease and no feasible control strategy, it is essential to have an efficient animal model which is representative of the natural route of infection as well as a viable treatment option. In this report, we evaluated the effect of different doses of M. paratuberculosis in their ability to colonize murine tissues following oral delivery and the ability of Lactobacillus casei ATCC 334, a nascent probiotic, to combat paratuberculosis. Oral inoculation of mice was able to establish paratuberculosis in a dose-dependent manner. Two consecutive doses of approximately 109 CFU per mouse resulted in a disseminated infection, whereas lower doses were not efficient to establish infection. All inoculated mice were colonized with M. paratuberculosis, maintained infection for up to 24 weeks post infection and generated immune responses that reflect M. paratuberculosis infection in cattle. Notably, oral administration of L. casei ATCC 334 did not reduce the level of M. paratuberculosis colonization in treated animals. Interestingly, cytokine responses and histology indicated a trend for the immunomodulation and reduction of pathology in animals receiving L. casei ATCC 334 treatment. Overall, a reproducible oral model of paratuberculosis in mice was established that could be used for future vaccine experiments. Although the L. casei ATCC 334 was not a promising candidate for controlling paratuberculosis, we established a protocol to screen other probiotic candidates.

Epidemiology and Management Strategies of Johne's disease in Endemic Situations

“…Click (2011) concluded from an experiment that Dietzia prebiotic can successfully treat the bovine paratuberculosis and can prevent JD development in MAP infected calves. Recently, lactic acid bacteria (LABATCC 334) have been used as probiotics for treatment of experimentally induced JD in mice (Cooney et al, 2014).…”

Characterization of the inflammatory phenotype of Mycobacterium avium subspecies paratuberculosis using a novel cell culture passage model

“…Mouse models are used to investigate the ability of MAP to invade the intestinal mucosa and disseminate to peripheral tissues (Bermudez et al, 2010), to determine preventive probiotics (Cooney et al, 2014) and to identify and validate vaccine candidates Scandurra et al, 2010). Unfortunately, mouse models offer limited insight on the complete disease progression, as mice do not exhibit intestinal inflammation in the same manner as ruminants in advanced stages of Johne's disease.…”

Mycobacterium avium subspecies paratuberculosis: An Emerging Bacterial Disease of Global Public Health Significance

“…Newborns are most susceptible to infection, and generally get infected early in their life (2 months of age) through ingestion of contaminated feed, water or milk from their infected mothers (Wang et al, 2014). In-utero infection has also been reported (Cooney et al, 2014). The disease represents a hidden threat for farmers.…”

“…MAP has wide host range and able to survive outside the host for long time (more than 9 months) and therefore it seems more insidious than any other bacteria to human and animal health (Cooney et al, 2014).…”

“…There is certainly evidence of an association (the occurrence at the same time and in the same patient of MAP and Crohn's disease) but not necessarily of causation (the organism has directly initiated the disease in the patient). Recent review concluded that, if MAP is involved in Crohn's disease, it is not mean that acting as a conventional infectious agent (Cooney et al, 2014). The objective of this review is to know the nature of Mycobacterium avium subspecies paratuberculosis in animals as well as to assess the public health and economic importance of the disease and to clarify the current thoughts on the possible relationship between MAP and CD.…”