Tissue remodeling by an opportunistic pathogen triggers allergic inflammation

Functional Recognition Theory and Type 2 Immunity: Insights and Uncertainties

“…The second prediction is that secreted products, such as bacterial toxins, that come from these functional classes may promote a type 2 immune pathway. This has recently been illustrated for the LasB metalloprotease toxin from Pseudomonas aeruginosa (89). The third prediction is that these broad classes of allergens would be sensed by shared pathways that detect alterations in host homeostasis or damage.…”

Pseudomonas aeruginosa: a pathogen making itself at home

“…No interests are declared. responses [2]. The net effect of these pathways is to promote enhanced mucus production, which the bacterium uses as a nutrient source, thereby maximizing its chances of survival and growth, ultimately colonizing the lungs [2].…”

“…This raises the intriguing possibility that using type 2 biologics might represent a novel strategy for treating chronic P. aeruginosa infection by targeting mucus production, thereby limiting bacterial growth. While Medzhitov's group in this study [2] is the first to describe bacterial immune deviation in detail, the ability to drive type 2 responses has also been reported for other bacteria, such as Staphylococcus aureus [8], making it an important aim to investigate whether other bacteria also use immune deviation as part of their survival strategy. This is of particular relevance for pathogens such as Haemophilus influenzae or Moraxella catarrhalis, which are known to cause exacerbations of chronic lung diseases such as chronic obstructive lung disease (COPD).…”

“…Type 2 responses encompass T H 2 cells and ILC2 capable of producing the cytokines IL-4, IL-5, and IL-13, which induce activation of eosinophils, basophils, and mast cells, and drive IgE generation; these have evolved to protect against helminths but also underlie allergic responses towards innocuous antigens in affected individuals [1]. In a recent study, Agaronyan et al [2] demonstrate that Pseudomonas aeruginosa, a gram-negative, opportunistic, ubiquitous environmental bacterium, can induce and augment type 2 immune responses and exploit host pathways for nutrient generation.…”

“…A comprehensive understanding of the molecular mechanisms underlying its pathogenesis is essential for the development of new putative treatments. Agaronyan and colleagues [2] demonstrated the unique ability of P. aeruginosa to divert the host immune system towards type 2 responses, revealing a relatively unexplored mechanism of bacterial immune evasion with the potential to provide a significant growth advantage to the pathogen. Consistent with this, an earlier study assessing the effect of chronic P. aeruginosa infection on the T H 1/T H 2 balance in bronchoalveolar lavage of patients with CF found that P. aeruginosa infection was associated with augmented type 2 cytokine concentrations [4].…”