MAP infection of ruminants (cattle, sheep, deer, goats etc.) causes severe weight loss, persistent diarrhea in some species, and death.
Much has been accomplished in understanding the interplay of MAP and its host in recent years using as new tools the genome of MAP and the many cellular, proteomic and reagents and assays recently developed. Despite this progress, core questions about MAP pathology remain unanswered:
Over the course of the disease, the extent of the tissue damage done by M. paratuberculosis varies. In early phases, no lesions may be detectable. In more advanced stages, lesions are found primarily in the gastrointestinal tract. The ileum may be thickened and corrugated and the neighboring lymph nodes are enlarged. Indications of the infection may be found through microscopic examination of the ileum or lymph nodes even if no signs are visible with the unaided eye.
- What is the minimally infective dose by animal species and age?
- Why are young ruminants much more susceptible than adult ruminants?
- What proportion of infected animals recover (clear the infection), if any?
- What factors affect MAP virulence?
- Are all MAP strains equally virulent?
- What are the innate immunologic responses to MAP infection in young animals?
Continued progress in comprehending host-MAP and MAP-environment dynamics is being made. Here is a summary of our current knowledge about the impact of a MAP infection on goat:
The target for MAP is the ruminant (such as a cow, goat, sheep, etc.) gastrointestinal tract. The most distal section, the ileum, is the primary site for infection. Ruminants swallow the organism (via MAP-contaminated milk, water or feed) which then invades through specialized ileal tissue called Peyer's patches to enter immune cells (macrophages) in the tissue. This microscopic infection of macrophages in the small intestinal persists for years without triggering any systemic response from the animal's immune system i.e., the animal is infected isn't sick and isn't responding to the infection in any visible way. At some point MAP spreads to lymph nodes flanking the gastrointestinal tract (the mesenteric nodes); later, for reasons not yet understood, the infection spreads throughout the ruminant. Clinical symptoms of Johne's disease usually begin to appear at this point, and the goat only now, often years after infection, reliably produces the signal of the infection detectable by blood tests (anti-MAP antibody in the serum and milk).
Throughout this long sub-clinical phase (estimated at 2-10 years) when the goat is apparently healthy although infected, it is capable of transmitting the infection by shedding MAP intermittently in milk and manure. When observable signs of illness finally begin, the rate and amount of shedding increases and the animal represents an ever greater risk to its own offspring and other young animals.
Infection of non-ruminant species is believed also to occur by swallowing MAP, for example carnivorous animals eating infected prey (e.g. stoat eating a rabbit infected through grazing contaminated grass) or an omnivore swallowing contaminated feed (crow pecking at seeds in contaminated rations). While evidence of infection (e.g. isolation of MAP from tissue) can be demonstrated, it is believed rare that the infection damages the intestinal tract or causes clinical disease of a non-ruminant.
MAP employs a variety of strategies to make sure it gets to where it can persist, and more importantly replicate, in an animal. One of these strategies is to use a component of the animal's defense system for its own home. After having been swallowed and travelled down the small intestine, MAP inveigles its way into the wall of the tract through “M” cells in the Peyer's patches and sets up residence within macrophages (immune cells) localized in that region to fight infection. Through complex cellular signaling and cytokine expression, MAP somehow turns off the bacteria-fighting mechanisms of the macrophages and instead creates a hospitable environment for itself. Far from alarming the immune system, this invasion seems to be ignored. No detectable lesions appear at this phase.
At some point, this intracellular pathogen triggers inflammation ("a protective tissue response to injury or destruction of tissues, which serves to destroy, dilute, or wall off both the injurious agent and the injured tissues"). Through production of various cytokines (gamma interferon being an important one) the body begins this cell-mediated immune response. More macrophages are recruited to the site of infection and form an ill-defined type of granuloma, an aggregate of living, dying and dead MAP and macrophages. This lesion progresses and regresses, but remains a localized battle in the gastrointestinal tract. As more MAP enter and replicate in the macrophages however, and as more cells are recruited to fight them, the lesion expands. This granulomatous inflammation spreads, and the infected macrophage may then depart the gastrointestinal tract for the neighboring lymph nodes, and be spread through the blood to other organ systems.
|In many respects the lesion resembles that of leprosy (i.e., lesions produced by infection with M. leprae) more than that of tuberculosis (two other diseases caused by mycobacteria). As in leprosy, some lesions may have myriad acid-fast (red) bacteria. Such lesions as shown on the right (red) are referred to as lepromatous or multi-bacillary. |
| ||This uncontrolled coalescing inflammation is the primary reason Johne's disease is fatal. The gastrointestinal tract is severely damaged and is no longer capable of absorbing nutrition so the cow keeps eating well but steadily loses weight. It is at this point that the cow begins to show signs of diarrhea or weight loss. In this latter stage of infection the intestine is usually thickened, corrugated and reddened; regional lymph nodes are swollen and pale. |