Biofilm-derived Legionella pneumophila evades the innate immune response in macrophages

Abstract

Legionella pneumophila, the causative agent of Legionnaire's disease, replicates in human alveolar macrophages to establish infection. There is no human-to-human transmission and the main source of infection is L. pneumophila biofilms established in air conditioners, water fountains, and hospital equipments. The biofilm structure provides protection to the organism from disinfectants and antibacterial agents. L. pneumophila infection in humans is characterized by a subtle initial immune response, giving time for the organism to establish infection before the patient succumbs to pneumonia. Planktonic L. pneumophila elicits a strong immune response in murine, but not in human macrophages enabling control of the infection. Interactions between planktonic L. pneumophila and murine or human macrophages have been studied for years, yet the interface between biofilm-derived L. pneumophila and macrophages has not been explored. Here, we demonstrate that biofilm-derived L. pneumophila replicates significantly more in murine macrophages than planktonic bacteria. In contrast to planktonic L. pneumophila, biofilm-derived L. pneumophila lacks flagellin expression, do not activate caspase-1 or -7 and trigger less cell death. In addition, while planktonic L. pneumophila is promptly delivered to lysosomes for degradation, most biofilm-derived bacteria were enclosed in a vacuole that did not fuse with lysosomes in murine macrophages. This study advances our understanding of the innate immune response to biofilm-derived L. pneumophila and closely reproduces the natural mode of infection in human.

Impact of Actinobacillus pleuropneumoniae biofilm mode of growth on the lipid A structures and stimulation of immune cells

“…66 Similarly, macrophages infected with Legionella pneumophila biofilm exhibited significantly lower levels of pro-inflammatory cytokine IL-1β, compared to those infected with planktonic bacteria. 67 In this way, biofilm-derived L.…”

Evasion of phagotrophic predation by protist hosts and innate immunity of metazoan hosts byLegionella pneumophila

“…When examining natural aquatic biofilms, L. pneumophila has been found with diverse Protists and metazoans, possibly as a parasite or as food (Abu Khweek & Amer, 2018; Abu Khweek et al, 2013; Rasch et al, 2016). Due to low detection of L. pneumophila in situ , infection of metazoans could not be determined (Rasch et al, 2016).…”

Legionellashows a diverse secondary metabolism dependent on a broad spectrum Sfp-type phosphopantetheinyl transferase

“…have a common association with water sources, surviving within amoebae, protozoa or slime moulds (Fields, Benson & Besser, 2002). Their association within microbial biofilm communities is also beneficial for their ability to survive and cause disease (Chaabna et al, 2013; Khweek et al, 2013). This close association between bacteria and protozoan host has led to a number of horizontal gene transfer events, significantly contributing to the intracellular fitness of these bacteria (Chien et al, 2004; Cazalet et al, 2004; Gimenez et al, 2011).…”