How Staphylococcus aureus and Pseudomonas aeruginosa Hijack the Host Immune Response in the Context of Cystic Fibrosis

Abstract

Cystic fibrosis (CF) is a serious genetic disease that leads to premature death, mainly due to impaired lung function. CF lungs are characterized by ongoing inflammation, impaired immune response, and chronic bacterial colonization. Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA) are the two most predominant bacterial agents of these chronic infections. Both can colonize the lungs for years by developing host adaptation strategies. In this review, we examined the mechanisms by which SA and PA adapt to the host immune response. They are able to bypass the physical integrity of airway epithelia, evade recognition, and then modulate host immune cell proliferation. They also modulate the immune response by regulating cytokine production and by counteracting the activity of neutrophils and other immune cells. Inhibition of the immune response benefits not only the species that implements them but also other species present, and we therefore discuss how these mechanisms can promote the establishment of coinfections in CF lungs.

Keywords: P. aeruginosa; S. aureus; cystic fibrosis; immune response.

Figure 1

Itaconate hijacking by SA and PA. (a) In normal circumstances, SA and PA are detected by TLR, leading to macrophage activation and inflammation induction via succinate oxidation. In order to modulate pro-inflammatory responses, itaconate is synthetized. Itaconate inhibits glycolysis, succinate oxidation and neutrophils degranulation, drastically reducing inflammation and protecting host cells. (b) During chronic infections, SA and PA are able to adapt and hijack host response. Despite bacterial glycolysis inhibition, itaconate induces PA growth by succinate accumulation which is used as energy source. Secondarily, itaconate leads to more EPS synthesis, enabling more biofilm formation, which in turn induces itaconate production, promoting SA PA persistency.

Figure 2

SA and PA anti-neutrophils effects, phagocytosis excluded.