China
Africa
Explore chapters and articles related to this topic
Host Defense II: Acquired Immunity
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
Mycobacteria bind C3b, but their cell walls are resistant to complememt lysis. They are phagocytosed via the complement receptor which does not induce the respiratory burst as do FcɤR. Thus, oxygen-dependent microbicidal mechanisms are less prominent. Mycobacteria also contain sulfatides, glycolipids which inhibit the fusion of phagosomes with lysosomes, and interfere with activation of intracellular killing. In addition, they have enzymes which neutralize reactive oxygen species, and they produce ammonia which neutralizes lysosomal pH. Some Leishmania secrete proteases (e.g., gp63 acid protease, acid phosphatase) which inactivate lysosomal enzymes, or inhibit generation of the respiratory burst. Leishmania also contain several enzymes such as superoxide dismutase which inactivates superoxide anion, and catalase which inactivates hydrogen peroxide. Leishmania surface lipophosphoglycan (LPG) inhibits generation of the respiratory burst, and is also an oxygen radical scavenger. LPG is also resistant to non-oxidative degradation, and the organism is adapted to growth at acidic pH. T. gondii may enter phagocytes via a non-FcR-mediated mechanism, and create a parasitophorous vacuole which is not acidified, and does not fuse with lysosomes. T. cruzi simply escapes from phagocytic vacuoles with a pore-forming protein and replicates in the cytoplasm.
Phosphonic Acids In Nature
Published in Richard L. Hilderbrand, The Role of Phosphonates in Living Systems, 2018
Richard L. Hilderbrand, Thomas O. Henderson
A working model for the structure of the two components of the lipophosphonoglycan has been proposed by Dearborn et al.80 on the basis of the composition and the constituents which fractionate together following partial hydrolysis. The fatty acids and phytosphingosine bases are proposed to be in ceramides, and the ceramides linked through acid hydrolyzable phosphate to inositol. The aminophosphonates may be involved in the linkage of the lipids, perhaps through inositol, and galactosamine may also be linked to inositol. One segment of both components may be an oligomeric lipid containing three inositol moieties and six aminophosphonates, with the sugar constituents varying for each component of the lipophosphonoglycan.80
Internalization of Microbial Pathogens by Integrin Receptors and the Binding of the Yersinia pseudotuberculosis Invasin Protein
Published in Yoshikazu Takada, Integrins: The Biological Problems, 2017
Evidence from Leishmania mexicana and the pathogenic yeast Histoplasma capsulatum indicates that the lectin-like activity may be shared by more than one integrin containing the β2 chain. In the case of Leishmania, macrophages and monocytes are able to bind to surfaces coated with abundant promastigote glycolipid lipophosphoglycan (LPG). Macrophages isolated from patients suffering from leukocyte adhesion deficiency (LAD), who are defective for synthesis of functional β2 chain integrins, are unable to bind LPG.53 Monoclonal antibodies directed specifically against either αmβ2, a150β2, or β2 chain alone were able to inhibit this binding, implying that multiple receptors are able to recognize the glycolipid. Peptides containing the tripeptide sequence arg-gly-asp, which normally inhibit the binding of complement to αmβ2, had no effect on binding LPG, indicating that the lectin site on the integrin receptor is distinct from the complement binding site.53 Similar results have been obtained for both the binding of Histoplasma capsulatum and Escherichia coli.54–56
Understanding Leishmania parasites through proteomics and implications for the clinic
Published in Expert Review of Proteomics, 2018
These events drive the adaptive changes in the parasite from a free-living form within the poikilothermic vector to an obligate intracellular form in the homeothermic mammalian host. Acclimatization of the parasite includes morphological, physiological, and biochemical modifications. Research on these changes has been supported by in vitro culture systems and further supported by genomics and transcriptomics to study the adaptive changes during differentiation. Some processes, such as trans-splicing and RNA editing, constitute the characteristic feature of protozoan parasite differentiation. The bite of the infected vector releases numerous substances that trigger the recruitment of neutrophils and subsequently macrophages to the skin. The parasite invades the neutrophils upon recognition, adhesion and invasion, which later serve as ‘Trojan horses’ for parasites. Subsequently, macrophages plays a vital role in the final establishment and amplification of infection [16]. This process of invasion also involves the parasite lipophosphoglycan (LPG) and gp63 [17], which interacts with different complement receptors and fibronectin receptors to facilitate phagocytosis [18]. The parasite then moves into the parasitophorous vacuole, where it undergoes differentiation into the amastigote form and proliferates. Upon intense multiplication, the macrophage ruptures and releases parasites into the tissue, which then invade new macrophages and/or are ingested by sand flies upon the next blood meal [19].
Calcium Signaling Commands Phagosome Maturation Process
Published in International Reviews of Immunology, 2019
Gourango Pradhan, Philip Raj Abraham, Rohini Shrivastava, Sangita Mukhopadhyay
Intracellular pathogens like Legionella sp., M. tuberculosis, Salmonella sp. and the protozoan parasite Leishmania sp. have the ability to inhibit acidification of phagosome by targeting either the recruitment of V-ATPases [127] to phagosome or by modulating the vesicular trafficking [112] such that acidic hydrolyzes are not able to reach to phagosomes. Salmonella factor GtgE can modulate the vesicular trafficking of Mannose 6 phosphate receptors (M6PR) to inhibit acidification of lysosomes [128]. Detailed study of Ca2+ signaling in modulation of phagosome acidification has been carried out in M. tuberculosis and Leishmania sp. M. tuberculosis inhibits the acidification of lysosomes by inhibiting the recruitment of V-ATPases. Mycobacterial cell wall components Mannose capped LAMs (ManLAM) and Phosphatidylmyo-inositol Mannosides (PIMs) [14,129] are shared by pathogenic mycobacteria such as M. avium and M. marinum but not by nonpathogenic M. smegmatis which contains Phosphatidylmyo-inositol capped LAM (PILAM) [130,131]. ManLAM and PIM are found to be associated with inhibition of P–L fusion process [132,133]. ManLAM has shown to inhibit EEA1 recruitment to the phagosomal membrane, delivery of Cathepsin D, and phagosome acidification [14,134]. EEA1 recruitment is essential in delivering H+-ATPase subunit Vo and hydrolases such as Cathepsin D from Trans-Golgi-Network (TGN) to the phagosomes. Notably, in contrast to PILAM, ManLAM limits Ca2+ influx in the cytosol, thereby favoring EEA1 recruitment and phagosome acidification [132]. Leishmania sp. exists as extracellular promastigotes in its vector where it resides and replicates as amastigotes within macrophages inside mammalian host [135]. Cross-talk of calcium signaling with phagosomal maturation in the case of Leishmania sp. mainly depends on PKC. PKC-dependent oxidative burst and protein phosphorylation were found to be markedly attenuated during Leishmania sp. infection [136,137]. PKC substrate MRP (MARCKS-related protein) levels were also found to be decreased during leishmania infection [138] (Figure 2c). Various studies have demonstrated that acidification of phagosomes is inhibited in leishmania-containing phagosomes and this is due to the integration of lipophosphoglycan (LPG) into lipid microdomains (LM) [136,139]. This process leads to the exclusion or loss of synaptogaminV which is an essential player in the recruitment of V-ATPases [140]. LPG also inhibits phagosomal maturation by blocking de-polymerization of F-actin [139] (Figure 2c). F-actin dynamics is very important for movement and fusion of phagosomes with upcoming vesicles and Ca2+ can directly influence actin dynamics via CaM/CaMKII and PKC.