The distribution of
iron and mycobacteria was examined in the intestinal tract of ruminants with naturally-occurring M.
paratuberculosis infection and compared with mycobacterial
infections in several species. This distribution was compared with that of
iron in chronic lesions caused by other microbial or parasitic agents. In the clinical form of
paratuberculosis in cattle, sheep and goats there was marked
lymphangiectasis and a high proportion of the granulomatous lesions contained siderotic macrophages with a high mycobacterial content. In cattle with preclinical lesions of granulomatous enteropathy, the greatest number of
acid-fast organisms was present in siderotic, non-differentiated, ileo-caecal macrophages; concurrent mast cell-associated allergic enteropathy was also apparent in the duodenum, proximal and mid-ileum of most animals. In
paratuberculosis-affected herds, a high proportion of non-productive cows were without classical granulomatous change but had cultural or immunological evidence of M.
paratuberculosis infection and similar allergic catarrhal enteropathy of the upper intestinal tract. Interstitial haemorrhage of the ileocaecal valve, with the accumulation of haemosiderin and
ferritin in undifferentiated macrophages was observed in some of these cattle and also in others with experimentally-induced
copper deficiency and acute
ostertagiasis. Colonisation of the ileo-caecal or caecal glandular crypts by large, apparently saprophytic
acid-fast organisms indicated regional tolerance to such organisms in all cattle. In other mycobacterioses such as bovine or
avian tuberculosis, undifferentiated, siderotic macrophages containing mycobacteria were also seen in early
granulomas, but epithelioid and giant cell differentiation invariably led to the disappearance of intracellular
iron and a reduction in mycobacterial numbers. In possums in which epithelioid and giant cells did not occur in response to M. bovis
infection,
siderosis persisted in many macrophages and overwhelming mycobacterial multiplication occurred. These studies indicate that, in most
infections with mycobacteria, differentiation of macrophages radically reverses their
iron acquisitive properties, creating an intracellular environment unsuitable for mycobacterial multiplication. It seems likely that allergically mediated microvascular haemorrhage, local tolerance of commensal mycobacteria and attenuation of the macrophage
siderosis reversal mechanism provide unique conditions for early, uninhibited, intracellular multiplication of M.
paratuberculosis in the ileo-caecal valve of certain mature ruminants.