Browsing by Author "Nono, Justin Komguep"

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    Open Access
    Proteomic Analysis of Excretory-Secretory Products of Mesocestoides corti Metacestodes Reveals Potential Suppressors of Dendritic Cell Functions
    (Public Library of Science, 2016) Vendelova, Emilia; De Lima, Jeferson Camargo; Lorenzatto, Karina Rodrigues; Monteiro, Karina Mariante; Mueller, Thomas; Veepaschit, Jyotishman; Grimm, Clemens; Brehm, Klaus; Hrčková, Gabriela; Lutz, Manfred B; Ferreira, Henrique B; Nono, Justin Komguep
    Author Summary: The metacestode larval stages of life-threatening tapeworms grow within the organs of its mammalian hosts, thus causing severe and long-lasting morbidity. Immunosuppression, which mainly depends on factors that are released or leaking from the parasite, plays an important role in both survival and proliferation of the larvae. These parasite-derived molecules are potential targets for developing new anti-parasitic drugs and/or improving the effectiveness of current therapies. Moreover, an optimized use of such factors could help to minimize pathologies resulting from uncontrolled immune responses, like allergies and autoimmune diseases. The authors herein demonstrate that larvae from a parasitic cestode release factors that sufficiently support the suppression of dendritic cells, a set of innate immune cells that recognizes and initiates host immune responses against invading pathogens. Employing modern analytic proteomic tools combined with immunological bioassays, several cestode-derived candidate immunomodulators were identified. This is the first bioassay-guided comprehensive library of candidate immunomodulators from a tissue-dwelling cestode larva. This work validates the unmet value of the Mesocestoides corti system in characterizing the mechanisms of host immunomodulation by metacestodes and reveals the largest database of candidate metacestode-derived immunomodulators until date.
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    The role of BATF2 during of experimental murine Schistosomiasis
    (2017) Mpotje, Thabo Rantanta Victor; Brombacher, Frank; Nono, Justin Komguep
    Schistosomiasis is one of the most debilitating tropical diseases with the potential to cause morbidity and mortality in infected populations unless well controlled. Current control measures are limited to treatment with praziquantel. A rather alarming situation given i) the inability of the drug to directly target the pathogenic eggs, ii) the emergence of praziquantel-resistant schistosomes, iii) the persistence of tissue fibro-proliferative destruction caused by the trapped parasite eggs, even after treatment. Intestinal and liver immunopathology are pathognomonic of schistosomiasis and generally result from the host inadequate Th2 and or Th17 responses to the egg-derived antigens. Failure to control these immune responses causes the most of the detriment to the infected host, highlighting the need for a better understanding of the regulatory mechanisms which might help prevent excessive immune responsiveness and the ensuing immunopathology. A Basic leucine zipper transcription factor ATF-like 2 (BATF2) which belongs to a family of transcription factors critical in the control of inflammatory responses has gained enormous momentum recently as a potential target to immune deregulation during cancer and infectious diseases. We reasoned that an eventual BATF2 influence on the host immune response during schistosomiasis might unveil its anti-disease potency and greatly facilitate the quest for a novel control strategy against the immunopathology during schistosomiasis. Addressing this in our present study, BATF2-deficient mice were used and characterized for immunological and physiological parameters during steady state and Schistosomiasis. Although the liver showed a reduced pro-fibrotic response, there was a notable increase of several pro-fibrotic cytokines (TNF-α, IFN-ƴ, TGF-β and IL-13) Which further translated into an elevated level of granulomatous inflammation and fibrosis in the gut of S. mansoni infected BATF-2-deficient mice when compared to the liver tissues of BATF2-deficient mice and both livers and intestines of infected littermate controls indicating that BATF2 appears to have a tissue-specific role on the regulation of fibrogranulomatous inflammation during schistosomiasis. Therefore, BATF2 has a critical, and hitherto unappreciated, role in mediating the regulation of gut fibrogranulomatous response so as to promote host survival during schistosomiasis.