Innate Immune Signaling Activated by MDR Bacteria in the Airway

Abstract

Health care-associated bacterial pneumonias due to multiple-drug resistant (MDR) pathogens are an important public health problem and are major causes of morbidity and mortality worldwide. In addition to antimicrobial resistance, these organisms have adapted to the milieu of the human airway and have acquired resistance to the innate immune clearance mechanisms that normally prevent pneumonia. Given the limited efficacy of antibiotics, bacterial clearance from the airway requires an effective immune response. Understanding how specific airway pathogens initiate and regulate innate immune signaling, and whether this response is excessive, leading to host-induced pathology may guide future immunomodulatory therapy. We will focus on three of the most important causes of health care-associated pneumonia, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae, and review the mechanisms through which an inappropriate or damaging innate immune response is stimulated, as well as describe how airway pathogens cause persistent infection by evading immune activation.

<b><i>Pseudomonas aeruginosa</i></b> and <b><i>Klebsiella</i></b> <b><i>pneumoniae</i></b> Adaptation to Innate Immune Clearance Mechanisms in the Lung

“…Transcriptomic analyses suggest that organisms that have acquired carbapenem resistance in vivo have a significantly altered pattern of gene expression [60]. The role of immune cells in the clearance of K. pneumoniae infection in the lung has been well characterized with the laboratory reference strain ATCC 43816 (KPPR1) recently reviewed [94]. However, current clinical isolates including the carbapenem-resistant ST258 clones [93] and the hvKP have many other genotypic and phenotypic changes.…”

The regulation of host defences to infection by the microbiota

“…Central to the coordination of all these airway defences is initial microbial recognition by pattern recognition receptors (PRRs) leading to the production of a variety of signalling molecules 52, 55. These include type I interferons during viral infection,56 and cytokines such as granulocyte–macrophage colony‐stimulating factor, interleukin‐22 (IL‐22), IL‐23 and IL‐17, which orchestrate both innate and adaptive antibacterial immunity 51, 52, 53, 57. Innate defences against infection have generally been considered ‘hard‐wired’ – a specific infection will elicit a defined, stereotypical immune response 58, 59, 60.…”

Розвиток Імунної Відповіді При Стафілококовій Пневмонії (Частина 3)

“…Продемонстрировано, что уже через 2 часа после инфицирования бактериями Staphylococcus aureus наблюдается усиление продукции IFN I типа клет-ками респираторного тракта [70,86,90].…”