epiglucan and Leishmaniasis--Cutaneous

American tegumentary leishmaniasis is a vector-borne parasitic disease caused by Leishmania protozoans. Innate immune cells undergo long-term functional reprogramming in response to infection or Bacillus Calmette-Guérin (BCG) vaccination via a process called trained immunity, conferring non-specific protection from secondary infections. Here, we demonstrate that monocytes trained with the fungal cell wall component β-glucan confer enhanced protection against infections caused by Leishmania braziliensis through the enhanced production of proinflammatory cytokines. Mechanistically, this augmented immunological response is dependent on increased expression of interleukin 32 (IL-32). Studies performed using a humanized IL-32 transgenic mouse highlight the clinical implications of these findings in vivo. This study represents a definitive characterization of the role of IL-32γ in the trained phenotype induced by β-glucan or BCG, the results of which improve our understanding of the molecular mechanisms governing trained immunity and Leishmania infection control.

Topics: Adult; Aged; Animals; BCG Vaccine; beta-Glucans; Bone Marrow Cells; Female; Hematopoietic Stem Cells; Humans; Immunity; Interleukin-1; Interleukins; Leishmania braziliensis; Leishmaniasis, Cutaneous; Macrophages; Male; Mice, Transgenic; Middle Aged; Monocytes; Signal Transduction; Transcription, Genetic; Up-Regulation; Vaccination; Young Adult

The beta-glucans derived from yeast cell walls have been reported for having many immunomodulatory activities in vivo and in vitro. In this study, Aureobasidium-derived soluble branched (1,3-1,6) beta-glucan (Sophy beta-glucan) was checked for natural killer (NK) activity and for the production of IFN-gamma and IL-4 in Leishmania amazonensis infection. The main experiment was performed with a group of female C57BL/6 and BALB/c mice, orally supplemented with 5% of Sophy beta-glucan and infected with promastogotes of L. amazonensis (1 x 10(7)) into the footpad. Increase in the footpad thickness with time was observed in BALB/c mice in spite of the oral Sophy beta-glucan supplement, but it was less in C57BL/6 mice. The difference in overall mean footpad thickness between 'infection only' versus 'infection + glucan' groups was statistically significant (P < 0.001). High NK activity in C57BL/6 than BALB/c mice was observed in 'glucan only' group compared to the control group and also in 'infection + glucan' group compared to 'infection only' group. The difference in the NK activity among these groups was significant (P < 0.05). The IFN-gamma level increased at weeks 7 and 8 post-infection in C57BL/6 mice and was significantly high in 'infection + glucan' group compared to the 'infection only' group (P < 0.05). IL-4 levels did not increase up to detectable levels throughout the study. The results led a conclusion that Sophy beta-glucan enhances NK activity and cellular immunity in L. amazonensis-infected mice.

Topics: Administration, Oral; Animals; Ascomycota; Cytotoxicity Tests, Immunologic; Female; Foot; Glucans; Immunologic Factors; Interferon-gamma; Interleukin-4; Killer Cells, Natural; Leishmania mexicana; Leishmaniasis, Cutaneous; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Severity of Illness Index; Time Factors