Bacterial lipid structural diversity mediates commensalism and pathogenesis

The human immune system must continuously distinguish between pathogenic bacteria and the numerous symbiotic bacteria that live in and on our bodies. In part, this distinction is driven by host sensing of specific lipid structures that comprise the bacterial membrane. Bacterial lipids from commensal and pathogenic bacteria alike are sensed via lipid recognition receptors, initiating downstream responses in the innate and adaptive immune systems. However, structural variations in the lipids from commensal bacteria tend to enable overall less stimulatory or more immunomodulatory outcomes following host recognition. This contributes to homeostatic immunity in their hosts, supporting normal immune development, proper immune responses and functional gut physiology. Conversely, in some pathogens, similar lipid modifications enable evasion or modulation of the immune system. Here, we review how the detection of pathogenic and commensal lipids via Toll-like receptor 2, Toll-like receptor 4 and CD1 lipid antigen presentation is mediated by bacterial lipid structure, with subsequent outcomes on host physiology.