Role of host- and pathogen-associated lipids in directing the immune response in mycobacterial infections, with emphasis onMycobacterium aviumsubsp.paratuberculosis

Abstract

Mycobacteria have a complex cell wall with a high lipid content that confers unique advantages for bacterial survival in the hostile host environment, leading to long-term infection. There is a wealth of evidence suggesting the role cell wall-associated lipid antigens play at the host-pathogen interface by contributing to bacterial virulence. One pathway that pathogenic mycobacteria use to subvert host immune pathways to their advantage is host cholesterol/lipid homeostasis. This review focuses on the possible role of pathogen- and host-associated lipids in the survival and persistence of pathogenic mycobacteria with emphasis on Mycobacterium avium subsp. paratuberculosis. We draw upon literature in diverse areas of infectious and metabolic diseases and explain a mechanism by which mycobacterial-induced changes in the host cellular energy state could account for phenomena that are a hallmark of chronic mycobacterial diseases.

Transcriptome Profiling of Bovine Macrophages Infected by Mycobacterium avium spp. paratuberculosis Depicts Foam Cell and Innate Immune Tolerance Phenotypes

“…There is a wealth of evidence suggesting the role of pathogenand host-associated lipids in the survival and persistence of pathogenic MAP (25). Interestingly, phagosome maturation and lysosomal fusion are affected only by living MAP, since dead bacilli cannot prevent these processes (18,26) similar to what is observed for Mycobacterium tuberculosis (27).…”

Mycobacterium avium subsp. paratuberculosis (Map) Fatty Acids Profile Is Strain-Dependent and Changes Upon Host Macrophages Infection

“…Previous studies highlighted a response of Mtb to the intramacrophage conditions by upregulating genes involved in lipid degradation or inhibiting lipid biosynthesis (Betts et al, 2002; Rengarajan et al, 2005; Mukhopadhyay et al, 2012). As Mtb, Map adapts to the intracellular environment in the macrophage, where the bacteria overcome exposure to cationic antimicrobial peptides, reactive oxygen species (ROS) and nutrient starvation, via the regulation of genes affecting its envelope's composition (Thirunavukkarasu et al, 2014). In fact, a different lipid profile was previously observed in the envelope of intracellular Map after 1 h of infection (Alonso-Hearn et al, 2010; Everman et al, 2015).…”

Immune Evasion Strategies of Pathogens in Macrophages: the Potential for Limiting Pathogen Transmission

“…Additionally, lipid bodies, also called lipid droplets, are lipid-rich organelles in the cytoplasm that regulate the storage and metabolism of neutral lipids (Martin and Parton, 2006;Bozza and Viola, 2010). Lipid is also an important component of the mycobacterial cell wall that provides unique advantages for bacterial survival and replication in the host environment, and acts as a permeability barrier against the entry of protons thus maintaining a constant pH in the bacteria (Tessema et al, 2001;Vergne et al, 2004;Thirunavukkarasu et a., 2014). Host abundant proteins related to immune regulators are composed of a variety of lipids, of which the pattern is altered based on different stages of the disease, and these adapt to the host immune responses (Rocha-Ramírez et al, 2008).…”