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Front Cell Infect Microbiol
2019 Jul 10;9:240. doi: 10.3389/fcimb.2019.00240.
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Intraspecies Polymorphisms in the Lipophosphoglycan of L. braziliensis Differentially Modulate Macrophage Activation via TLR4.
Vieira TDS
,
Rugani JN
,
Nogueira PM
,
Torrecilhas AC
,
Gontijo CMF
,
Descoteaux A
,
Soares RP
.
Abstract
Lipophosphoglycan (LPG) is the major Leishmania surface glycoconjugate having importance during the host-parasite interface. Leishmania (Viannia) braziliensis displays a spectrum of clinical forms including: typical cutaneous leishmaniasis (TL), mucocutaneous (ML), and atypical lesions (AL). Those variations in the immunopathology may be a result of intraspecies polymorphisms in the parasite''s virulence factors. In this context, we evaluated the role of LPG of strains originated from patients with different clinical manifestations and the sandfly vector. Six isolates of L. braziliensis were used: M2903, RR051 and RR418 (TL), RR410 (AL), M15991 (ML), and M8401 (vector). LPGs were extracted and purified by hydrophobic interaction. Peritoneal macrophages from C57BL/6 and respective knock-outs (TLR2-/- and TLR-4-/-) were primed with IFN-γ and exposed to different LPGs for nitric oxide (NO) and cytokine production (IL-1β, IL-6, IL-12, and TNF-α). LPGs differentially activated the production of NO and cytokines via TLR4. In order to ascertain if such functional variations were related to intraspecies polymorphisms in the LPG, the purified glycoconjugates were subjected to western blot with specific LPG antibodies (CA7AE and LT22). Based on antibody reactivity preliminary variations in the repeat units were detected. To confirm these findings, LPGs were depolymerized for purification of repeat units. After thin layer chromatography, intraspecies polymorphisms were confirmed especially in the type and/size of sugars branching-off the repeat units motif. In conclusion, different isolates of L. braziliensis from different clinical forms and hosts possess polymorphisms in their LPGs that functionally affected macrophage responses.
Figure 3. Western blot of purified lipophosphoglycan (LPG). Purified LPG (10 μg per lane) from promastigotes of L. braziliensis strains (M2903, RR051, RR418, RR410, M15991, and M8401) were incubated with the antibody CA7AE (1:1,000) (A) and LT22 (1:1,000) (B). LPG purified from L. braziliensis M2903 strain was used as positive control. TL, Typical lesions; AL, Atypical lesions; ML, Mucocutaneous strain; VEC, Vector strain.
Figure 4. Thin layer chromatography (TLC) of dephosphorylated [3H]Gal-repeat units obtained from different L. braziliensis LPGs. (A) M15991 repeat units and (B) M8401 repeat units. Gal, galactose; Man, mannose.
Figure 5. Thin layer chromatography (TLC) of dephosphorylated [3H]Gal-repeat units obtained from different L. braziliensis LPGs. (A) M2903 repeat units, (B) RR410, and (C) RR051 treated (open circles) or not (closed circles) with β-glucosidase. Glc, glucose; Gal, galactose; Man, mannose.
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