The requirement of cholesterol for internalization of eukaryotic pathogens like protozoa (Leishmaniasis, Malaria and Toxoplasmosis) and the exchange of cholesterol along with other metabolites during reproduction in Schistosomes (helminths) under variable circumstances are poorly understood. In patients infected with some other helminthes, alterations in the lipid profile have been observed. Also, the mechanisms involved in lipid changes especially in membrane proteins related to parasite infections remain uncertain. Present review of literature shows that parasites induce significant changes in lipid parameters, as has been shown in the in vitro study where substitution of serum by lipid/cholesterol in medium and in experimental models (in vivo). Thus changes in lipid profile occur in patients having active infections with most of the parasites. Membrane proteins are probably involved in such reactions. All parasites may be metabolising cholesterol, but the exact relationship with pathogenic mechanism is not clear. So far, studies suggest that there may be some factors or enzymes, which allow the parasite to breakup and consume lipid/cholesterol. Further studies are needed for better understanding of the mechanisms involved in vivo. The present review analysis the various studies till date and the role of cholesterol in pathogenesis of different parasitic infections.


During infection significant alterations in lipid metabolism and lipoprotein composition occur. Triglyceride and VLDL cholesterol levels increase, while reduced HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) levels are observed. More importantly, endotoxemia modulates HDL composition and size: phospholipids are reduced as well as apolipoprotein (apo) A-I, while serum amyloid A (SAA) and secretory phospholipase A2 (sPLA2) dramatically increase, and, although the total HDL particle number does not change, a significant decrease in the number of small- and medium-size particles is observed. Low HDL-C levels inversely correlate with the severity of septic disease and associate with an exaggerated systemic inflammatory response. HDL, as well as other plasma lipoproteins, can bind and neutralize Gram-negative bacterial lipopolysaccharide (LPS) and Gram-positive bacterial lipoteichoic acid (LTA), thus favoring the clearance of these products. HDLs are emerging also as a relevant player during parasitic infections, and a specific component of HDL, namely, apoL-1, confers innate immunity against trypanosome by favoring lysosomal swelling which kills the parasite. During virus infections, proteins associated with the modulation of cholesterol bioavailability in the lipid rafts such as ABCA1 and SR-BI have been shown to favor virus entry into the cells. Pharmacological studies support the benefit of recombinant HDL or apoA-I mimetics during bacterial infection, while apoL-1–nanobody complexes were tested for trypanosome infection. Finally, SR-BI antagonism represents a novel and forefront approach interfering with hepatitis C virus entry which is currently tested in clinical studies. From the coming years, we have to expect new and compelling observations further linking HDL to innate immunity and infections.

Table 1

Mechanisms of parasite–microbiota interactions in the vertebrate gut.

Mechanism category Host factors involved Effect direction Mechanism description (Potential) Consequences Examples showing both mechanism and consequence
Physical changes to the gut Intestinal mucus P > M Helminths, and some protozoa, increase mucus production Increases mucolytic bacteria and bacteria capable of using mucins as a carbon source T. suis (Li et al., ); T. muris (Holm et al., ; Houlden et al., ; Ramanan et al., ); Eimeria (Collier et al., )
Reduces bacteria attachment to the gut epithelium T. trichiura (Broadhurst et al., )
Parasites alter mucus composition and structure Alters food availability, attachment sites, gut flow rates, and access to the epithelium for gut microbes T. muris (Hasnain et al., ); N. brasiliensis(Tsubokawa et al., ); E. histolytica (Hicks et al., ); T. gondii (Kim and Khan, ; Trevizan et al., ); Giardia (Kim and Khan, )
M > P Microbiota affects mucus synthesis Impacts expulsion rate of parasites
Epithelial barrier P > M Parasites damage epithelial tight junctions Allows for microbial translocation across the gut epithelium H. polygyrus (Chen et al., ); T. spiralis (McDermott et al., ); S. venezuelensis(Farid et al., ); N. brasiliensis (Hyoh et al., ); T. gondii (Heimesaat et al., ; Hand et al., ; Cohen and Denkers, ); Giardia (Chen et al., ; Halliez, )
M > P Microbiota strengthens and shapes permeability of mucus barrier Alters the degree of mucosal damage and bacterial translocation that occurs after parasite infection
Epithelial cell turnover P > M Helminths increase epithelial cell turnover Selects for microbes capable of replicating at a high rate
M > P Microbiota mediate cell turnover via SCFAs Impacts parasite colonization and expulsion
Innate immunity Toll-like receptors P > M Helminths increase expression of TLRs Increases activation of responses against microbiota H. polygyrus (Ince et al., ; Friberg et al., ); H. diminuta (Kosik-Bogacka et al., )
M > P Microbiota can prime protective immune responses through TLRs Protects against parasite infection through primed innate immune responses T. gondii (Benson et al., )
Antimicrobial peptides P > M Helminths secrete antimicrobial peptides Protects against harmful immune responses elicited by microbial contact
Inflammasomes P > M Parasites alter inflammasome activation Alters pro-inflammatory cytokine secretion and microbial dysbiosis T. musculis (Chudnovskiy et al., )
M > P Microbiota-derived metabolites activate inflammasomes Creates a pro-inflammatory environment that may aid protozoa clearance, but also increased helminth chronicity
Adaptive immunity Th2 cells P > M Helminths increase Th2 responses Alters mucosal barrier function and impairs TH1 responses leading to an inability to control bacterial replication H. polygyrus (Chen et al., )
M > P Gut microbes inhibit or enhance Th2 responses Alters parasite survival T. muris (Dea-Ayuela et al., )
Treg cells P > M Helminths increase Treg responses Downregulates inflammatory responses against microbiota
Promotes Treg-inducing species H. polygyrus (Reynolds et al., )
Helminths secrete TGF-β mimics to induce Foxp3+ Tregs Downregulates inflammatory responses against microbiota H. polygyrus and T. circumcincta (Grainger et al., )
M > P Gut microbes induce Treg responses Impacts parasite persistence and survival H. polygyrus (Reynolds et al., ; Ohnmacht et al., )
Physical attachment n/a M > P Helminth egg hatching require/is enhanced by bacteria attachment Increases helminth colonization T. muris (Hayes et al., ); T. suis (Vejzagić et al., )
Heterophagy n/a M > P Pathogenic bacteria phagocytosed by parasite induces virulence Increases parasite virulence E. histolytica (Galván-Moroyoqui et al., )
Endosymbiosis n/a M > P Enteric bacteria engulfed by parasite, but not ingested Alters host-parasite immune interaction Giardia (El-Shewy and Eid, )
Secretions n/a P > M Helminth body fluids/secretions have antibacterial and bacteriolytic properties Disrupts microbiota
M > P Gut microbes secrete molecules that inhibit invading parasites Decreases parasite infections Cryptosporidium (Deng et al., ; Foster et al., ; Glass et al., ); Giardia(Pérez et al., ); E. tenella(Tierney et al., )
Ingestion n/a P > M Helminths ingest bacteria from their gut environment Restructures microbiota communities T. muris (White et al., )