Lipophosphoglycan_coat Leishmania

1 lipophosphoglycan coat

1.1 structure
1.2 function
1.3 intracellular mechanism of infection
1.4 uptake , survival
1.5 persistency , attraction
1.6 silent phagocytosis theory

lipophosphoglycan coat

leishmania possesses lipophosphoglycan coat on outside of cell. lipophosphoglycan trigger toll-like receptor 2, signalling receptor involved in triggering innate immune response in mammals.

structure

the precise structure of lipophosphoglycan varies depending on species , lifecycle stage of parasite. glycan component particularly variable , different lipophosphoglycan variants can used molecular marker different lifecycle stages. lectins, group of plant proteins bind different glycans, used detect these lipophosphoglycan variants. example, peanut agglutinin binds particular lipophosphoglycan found on surface of infective form of l. major.

function

lipophosphoglycan used parasite promote survival in host , mechanisms parasite center around modulating immune response of host. vital, leishmania parasites live within macrophages , need prevent macrophages killing them. lipophosphoglycan has role in resisting complement system, inhibiting oxidative burst response, inducing inflammation response , preventing natural killer t cells recognising macrophage infected leishmania parasite.

intracellular mechanism of infection

in order avoid destruction immune system , thrive, leishmania hides inside host s cells. location enables avoid action of humoral immune response (because pathogen safely inside cell , outside open bloodstream), , furthermore may prevent immune system destroying host through nondanger surface signals discourage apoptosis. primary cell types leishmania infiltrates phagocytotic cells such neutrophils , macrophages.

usually, phagocytotic immune cell macrophage ingest pathogen within enclosed endosome , fill endosome enzymes digest pathogen. however, in case of leishmania, these enzymes have no effect, allowing parasite multiply rapidly. uninhibited growth of parasites overwhelms host macrophage or other immune cell, causing die.

transmitted sandfly, protozoan parasites of l. major may switch strategy of first immune defense eating/inflammation/killing eating/no inflammation/no killing of host phagocyte , corrupt own benefit. use willingly phagocytosing polymorphonuclear neutrophil granulocytes (pmns) rigorously tricky hideout, proliferate unrecognized immune system , enter long-lived macrophages establish hidden infection.

uptake , survival

lifecycle of leishmania

upon microbial infection, pmns move out bloodstream through vessels’ endothelial layer, site of infected tissue (dermal tissue after fly bite). initiate first immune response , phagocytize invader recognition of foreign , activating surfaces on parasite. activated pmn secrete chemokines, il-8 particularly, attract further granulocytes , stimulate phagocytosis. further, l. major increases secretion of il-8 pmns. mechanism observed during infection other obligate intracellular parasites, well. microbes these, multiple intracellular survival mechanisms exist. surprisingly, coinjection of apoptotic , viable pathogens causes far more fulminate course of disease injection of viable parasites. when anti-inflammatory signal phosphatidylserine found on apoptotic cells, exposed on surface of dead parasites, l. major switches off oxidative burst, thereby preventing killing , degradation of viable pathogen.

in case of leishmania, progeny not generated in pmns, in way can survive , persist untangled in primary site of infection. promastigote forms release leishmania chemotactic factor (lcf) actively recruit neutrophils, not other leukocytes, instance monocytes or nk cells. in addition that, production of interferon gamma (ifnγ)-inducible protein 10 (ip10) pmns blocked in attendance of leishmania, involves shut down of inflammatory , protective immune response nk , th1 cell recruitment. pathogens stay viable during phagocytosis since primary hosts, pmns, expose apoptotic cell-associated molecular pattern (acamp) signaling no pathogen .

persistency , attraction

the lifespan of neutrophil granulocytes quite short. circulate in bloodstream 6 10 hours after leaving bone marrow, whereupon undergo spontaneous apoptosis. microbial pathogens have been reported influence cellular apoptosis different strategies. because of inhibition of caspase3-activation, l. major can induce delay of neutrophils apoptosis , extend lifespan @ least 2–3 days. fact of extended lifespan beneficial development of infection because final host cells these parasites macrophages, migrate sites of infection within 2 or 3 days. pathogens not dronish; instead take on command @ primary site of infection. induce production pmns of chemokines mip-1α , mip-1β (macrophage inflammatory protein) recruit macrophages.

silent phagocytosis theory

to save integrity of surrounding tissue toxic cell components , proteolytic enzymes contained in neutrophils, apoptotic pmns silently cleared macrophages. dying pmns expose eat me -signal phosphatidylserine transferred outer leaflet of plasma membrane during apoptosis. reason of delayed apoptosis, parasites persist in pmns taken macrophages, employing absolutely physiological , nonphlogistic process. strategy of silent phagocytosis has following advantages parasite:

taking apoptotic cells silences macrophage killing activity leading survival of pathogens.
pathogens inside of pmns have no direct contact macrophage surface receptors, because can not see parasite inside apoptotic cell. so, activation of phagocyte immune activation not occur.

however, studies have shown unlikely, pathogens seen leave apoptopic cells , no evidence known of macrophage uptake method.