No abstract

SUMMARYThe relative virulence of different isolates of Mycobacterium avium has been linked to their capacity to trigger the secretion of TNF from the macrophages they infect. H37Ra, which is very active in inducing TNF release due to its lipoarabinomannan moiety, was used to compare with the previous results. The growth ofH37Ra in macrophages was increased in vitro by the neutralization of TNF and neutralization of either TNF and/or interferon-gamma (IFN-I') enhanced the in vivo proliferation of this microbe in the spleen and liver of infected animals, whereas only the combination of both anti-TNF and anti-IFN-I' enhanced bacterial proliferation in the lung. We conclude that resistance to the avirulent strains of Myco. avium did not involve TNF, but rather antimicrobial mechanisms expressed consitutively in the mononuclear phagocytes. In contrast, TNF plays an important role in the control of Myco. tuberculosis H37Ra infection.

We studied the ability of two Mycobacterium avium strains with different virulences to induce tumor necrosis factor alpha (TNF) synthesis by mouse resident peritoneal macrophages (RPM) in vitro in an experiment to look for a possible correlation between virulence and this TNF-inducing capacity. The low-virulence strain, 1983, induced significantly higher production of TNF by RPM than did the high-virulence strain, ATCC 25291. TNF neutralization during culture of infected RPM resulted in enhancement of growth of strain 1983 and had no effect on growth of strain ATCC 25291; TNF treatment of strain ATCC 25291-infected macrophages had no effect on mycobacterial growth. The extent of M. avium growth and the amount of TNF synthesis were independent of the presence of contaminating T cells or NK cells in the macrophage monolayers. Intraperitoneal administration of anti-TNF monoclonal antibodies to BALB/c mice infected intravenously with M. avium 1983 abrogated the elimination of the bacteria in the liver and caused a slight increase in bacterial growth in the spleen. Neutralization of TNF led to a minor increase in the proliferation of M. avium ATCC 25291 in the liver and spleen of BALB/c mice late in infection. Anti-TNF treatment did not affect the growth of the two M. avium strains in BALB/c.Bcg r (C.D2) mice, suggesting that restriction of M. avium growth in these mycobacterium-resistant mice is TNF independent. In conclusion, the capacity of certain avirulent M. avium strains to induce TNF production by macrophages may limit their ability to proliferate both in vitro and in vivo.

Mycobacterium avium subsp. paratuberculosis (MAP) and adherent-invasive Escherichia coli (AIEC) have been implicated as primary triggers in Crohn's disease (CD). In this study, we evaluated the prevalence of MAP and E. coli (EC) DNA in peripheral blood from 202 inflammatory bowel disease (IBD) patients at various disease periods and compared against 24 cirrhotic patients with ascites (CIR) (non-IBD controls) and 29 healthy controls (HC). MAP DNA was detected by IS900-specific nested PCR, EC DNA by malB-specific nested PCR and AIEC identity, in selected samples, by sequencing of fimH gene. CD patients with active disease showed the highest MAP DNA prevalence among IBD patients (68 %). Infliximab treatment resulted in decreased MAP detection. CIR patients had high individual and coinfection rates (75 % MAP, 88 % EC and 67 % MAP and EC), whilst HC controls had lower MAP prevalence (38 %) and EC was undetectable in this control group. EC DNA prevalence in IBD patients was highly associated with CD, and 80 % of EC from the selected samples of CD patients analyzed carried the fimH30 allele, with a mutation strongly associated with AIEC. Our results show that coinfection with MAP and AIEC is common and persistent in CD, although the high MAP and EC detection in CIR patients suggested that colonization is, at least, partially dependent on increased gut permeability. Nevertheless, facilitative mechanisms between a susceptible host and these two potential human pathogens may allow their implication in CD pathogenesis.