Chapter 23 : Differential Cytokine Response Following Challenge of A/J Mice with Virulent and Avirulent Legionella pneumophila

Abstract:

Legionella pneumophila causes a severe atypical pneumonia in humans, the so-called Legionnaires' disease. Although the disease mostly occurs in immunocompromised subjects, several virulence factors of Legionella have been described that confer to the microorganism an intrinsic aggressive potential. The ability of this pathogen to replicate in host macrophages is considered a major virulence trait. For this reason, the susceptibility to the experimental infection with L. pneumophila observed in guinea pigs and in selected mouse strains has been generally explained by the permissiveness of macrophages of these animals for Legionella invasion and intracellular replication in vitro, as reported, for elicited peritoneal macrophages from susceptible A/J mice. Researchers found that the i.p. inoculation of virulent Legionella cells from the VIR+ strain was rapidly lethal for A/J mice, since 100 and 60% of the animals acutely died within 2 days following the challenge with 2 X 108 or 2 X 107 bacterial cells. Unchecked TNF-α production upon i.v. Legionella inoculation has recently been reported as the causative factor in the death of Legionella replication-unpermissive BALB/c mice. Accordingly, the protection afforded by IL-10 treatment or TNF-α neutralization in the mice model also indicates that the release of TNF-α, a well-known toxic shock-related cytokine, plays a major role in mediating the lethal effects of the virulent legionellae. Therefore induction of proinflammatory cytokines, in particular TNF-α, besides being an important factor facilitating the resolution of L. pneumophila infections, might also be regarded as a possible contributory factor to the pathogenic action of virulent L. pneumophila strains.