Interleukin‐1 deficiency in combination with macrophage depletion increases susceptibility to Pseudomonas aeruginosa bacteremia

Abstract

We evaluated the role of IL-1 during Pseudomonas aeruginosa bacteremia by intravenously injecting P. aeruginosa strain D4 into IL-1-deficient and WT mice. The two strains showed equivalent mortality rates. However, when the mice were pretreated with cyclophosphamide, bacteremia-induced mortality was significantly greater in the IL-1-deficient mice than in the WT mice (P < 0.01). We then investigated the role of neutrophils and macrophages in protecting IL-1-deficient mice from bacteremia by administering anti-Gr-1 antibody or liposomes containing dichloromethylene diphosphonate, respectively. After P. aeruginosa inoculation survival was significantly lower in the macrophage-depleted IL-1-deficient mice than in the WT mice. In contrast, neutrophil depletion did not have this effect. Compared to the macrophage-depleted WT mice, the macrophage-depleted IL-1-deficient bacteremic mice had higher bacterial counts in various organs 48 and 72 hr post-infection. They also had lower TNF-α, IL-6, and INF-γ concentrations in their livers during the early phase of sepsis. Thus, IL-1 deficiency becomes disadvantageous during P. aeruginosa bacteremia when it is accompanied by immunosuppression, particularly when macrophage functions are seriously impaired. macrophage depletion, neutropenia, Pseudomonas aeruginosa. Of all the proinflammatory cytokines that are evoked by bacterial infections, IL-1 is one of the most important. We have previously shown that IL-1-deficient mice are more susceptible than WT mice to gut-derived sepsis arising from P. aeruginosa infection (1). In this model, bacterial translocation from the gastrointestinal tract was inCorrespondence Key words

Cochlin Produced by Follicular Dendritic Cells Promotes Antibacterial Innate Immunity

“…These data confirm previous studies describing that the recruitment of neutrophils and macrophages to the lung is absolutely critical for the outcome of P. aeruginosa infection and that blunted early local inflammatory response in the lung leads to later higher bacteria load, uncontrolled systemic cytokine secretion and reduced survival (Horino et al, 2009; Koh et al, 2009). Taken together, our study demonstrates an unexpected function of FDC in modulating innate immunity and a role for secondary lymphoid organ and particularly local lymph nodes in the amplification of the innate immune response by the release of modulators such as cochlin.…”

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