Mycobacterium avium complex

MAC group generalities

• Share many of the same properties, so often referred to as the M.avium-intracellulare complex (MAIC)
• Dogs and cats very resistant to infection with MAIC
  • Siamese cats are predisposed to getting disseminated disease.
• Ubiquitous, saprophytic causing disease in immunocompromised hosts.
• Genetic susceptibility for disseminated disease in:
  • Humans, rabbits, Basset hounds and mice
    • Susceptibility identified by the Bcg locus in mice.
• In most mammals infection results in granulomatous inflammation with little necrosis, calcification or fibrosis. Lymph nodes are usually involved. Dissemination by hematogenous route later.

Johne's disease

• Caused by Mycobacterium avium subsp. paratuberculosis
• Faculative intracellular acid-fast bacillus
• Rule out Nocardia and Corynebacterium – also acid-fast.
• 22% of the US dairy herds are infected.
• Infection can be cleared at the early stage, but if colonization takes place, and initial subclinical phase and then a chronic phase.
• Clinical signs – chronic diarrhea, progressive emaciation – diffuse granulomatous enteritis and lymphadenitis.
• Progression to clinical stages associated with reduced expression of IFNgamma at the site of infection.
• Infected at an early age, c/s not apparent until 2yrs+ old.
• Will shed the bacteria in the faeces before c/s apparent.
• Infection mediated by transport of bacteria across the Peyer’s patch by M cells and macrophages – transported inside macrophages
• CMI is mainly by αβ T cells including CD4+ T cells and CD8+ T cells.
• γδ T cells involved in protection of early infectious stage of disease of mycobacteria and other intracellular organisms
• Proliferation and activation of γδ T cells at the site of colonization is mediated by 70kd mycobacterial heat shock protein and cytokines.
• γδ T cells produce proinflammatory cytokines, activate immunoreactive macrophages, αβ T cells and NK cells.
• But much controversy of their protective role or whether they just recruit other inflammatory cells.

This study: BALB/c mice are susceptible to M.paratuberculosis infection γδ T cells KO mice produced fewer granulomas than controls and lower numbers of organisms in the spleen. Therefore γδ T cells may be involved in granuloma formation γδ T cells in bovines produce TH1 type of cytokines – IFNγ, TNFα and IL-2. May recruit macrophages via production of MCP-1. TNFα and IFNγ act synergysticly to produce granulomas. IL-2 induces proliferation of T cells, B cells, macrophages and NK cells, and enhances IFNγ and TNFα production from CD4+ T cells. Bovines have relatively high proportion of γδ T cells in the GIT compared to man and mice.

[Reduced formation of granulomata in gamma-delta T cell knockout BALB/c mice inoculated with Mycobacterium avium subsp. Paratuberculosis. Tanaka S et al. Vet Path (2000) 37 415-21]

• Can use culture to detect the bacteria in pooled fecal samples from low-level infected herds – as sensitive as detection of Mycobacteria avium subsp. paratuberculosis from feces of an individual animal (about 70%)

[Culture of pooled bovine fecal samples as a method to screen herds for paratuberculosis. JVDI (2000) 12 547-51] [Immunohistochemical detection of M.paraTB in formalin fixed tissues. JVDI (2000) 12 60-3]

• The subclinical form in sheep – intestinal lymphoid tissue or adjacent lamina propria.
• Numbers of organisms identifiable in macrophages seen in lesions with least CMI response.