Macrophage-infectivity potentiator of Trypanosoma cruzi (TcMIP) is a new pro-type 1 immuno-stimulating protein for neonatal human cells and vaccines in mice.
Radwanska, Magdalena; De Lemos Esteves, Frédéric; Linsen, Loeset al.
[en] This work identifies the protein "macrophage infectivity potentiator" of Trypanosoma cruzi trypomastigotes, as supporting a new property, namely a pro-type 1 immunostimulatory activity on neonatal cells. In its recombinant form (rTcMIP), this protein triggers the secretion of the chemokines CCL2 and CCL3 by human umbilical cord blood cells from healthy newborns, after 24h in vitro culture. Further stimulation for 72h results in secretion of IFN-γ, provided cultures are supplemented with IL-2 and IL-18. rTcMIP activity is totally abolished by protease treatment and is not associated with its peptidyl-prolyl cis-trans isomerase enzymatic activity. The ability of rTcMIP to act as adjuvant was studied in vivo in neonatal mouse immunization models, using acellular diphtheria-tetanus-pertussis-vaccine (DTPa) or ovalbumin, and compared to the classical alum adjuvant. As compared to the latter, rTcMIP increases the IgG antibody response towards several antigens meanwhile skewing antibody production towards the Th-1 dependent IgG2a isotype. The amplitude of the rTcMIP adjuvant effect varied depending on the antigen and the co-presence of alum. rTcMIP did by contrast not increase the IgE response to OVA combined with alum. The discovery of the rTcMIP immunostimulatory effect on neonatal cells opens new possibilities for potential use as pro-type 1 adjuvant for neonatal vaccines. This, in turn, may facilitate the development of more efficient vaccines that can be given at birth, reducing infection associated morbidity and mortality which are the highest in the first weeks after birth.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Radwanska, Magdalena; Laboratory of Parasitology, Faculty of Medicine, and ULB Center for Research in Immunology (UCRI), Université Libre de Bruxelles (ULB), Brussels, Belgium
De Lemos Esteves, Frédéric ; Université de Liège - ULiège > Centres généraux > CARE Digital Tools | Outils numériques
Linsen, Loes; Laboratory of Parasitology, Faculty of Medicine, and ULB Center for Research in Immunology (UCRI), Université Libre de Bruxelles (ULB), Brussels, Belgium
Coltel, Nicolas; Laboratory of Parasitology, Faculty of Medicine, and ULB Center for Research in Immunology (UCRI), Université Libre de Bruxelles (ULB), Brussels, Belgium
Cencig, Sabrina; Laboratory of Parasitology, Faculty of Medicine, and ULB Center for Research in Immunology (UCRI), Université Libre de Bruxelles (ULB), Brussels, Belgium
Widart, Joëlle ; Université de Liège - ULiège > Département de pharmacie
Massart, Anne-Cécile ; Université de Liège - ULiège > Département de chimie (sciences) > Center for Analytical Research and Technology (CART)
Colson, Séverine ; Université de Liège - ULiège > Centres généraux > Centre d'ingénierie des protéines
Di Paolo, Alexandre; Center for Protein Engineering (CIP), Université de Liège (ULg), Liège, Belgium
Percier, Pauline; Laboratory of Parasitology, Faculty of Medicine, and ULB Center for Research in Immunology (UCRI), Université Libre de Bruxelles (ULB), Brussels, Belgium
Ait Djebbara, Sarra; Laboratory of Parasitology, Faculty of Medicine, and ULB Center for Research in Immunology (UCRI), Université Libre de Bruxelles (ULB), Brussels, Belgium
Guillonneau, François ; Université de Liège - ULiège > Département de chimie (sciences) > Chimie analytique inorganique
Flamand, Véronique; Institute for Medical Immunology (IMI), and ULB Center for Research in Immunology (U-CRI), Gosselies, Belgium
De Pauw, Edwin ; Université de Liège - ULiège > Département de chimie (sciences)
Frère, Jean-Marie ; Université de Liège - ULiège > Département des sciences de la vie > Centre d'Ingénierie des Protéines (CIP)
Carlier, Yves; Laboratory of Parasitology, Faculty of Medicine, and ULB Center for Research in Immunology (UCRI), Université Libre de Bruxelles (ULB), Brussels, Belgium ; Department of Tropical Medicine, School of Public Health and Tropical Medicine, Tulane University, New Orleans, MA, United States
Truyens, Carine; Laboratory of Parasitology, Faculty of Medicine, and ULB Center for Research in Immunology (UCRI), Université Libre de Bruxelles (ULB), Brussels, Belgium
Macrophage-infectivity potentiator of Trypanosoma cruzi (TcMIP) is a new pro-type 1 immuno-stimulating protein for neonatal human cells and vaccines in mice.
FWB - Fédération Wallonie-Bruxelles ULB - Université Libre de Bruxelles F.R.S.-FNRS - Fonds de la Recherche Scientifique
Funding text :
Financial support was provided by The Fédération Wallonie-Bruxelles (FWB – grant 041/5892), The Fonds de Maturation of ULB (grant AdjuvacII), The Fonds d’Encouragement à la Recherche (ULB), the Fonds Emile Defay (ULB), the Fonds David et Alice Van Buuren (ULB), and the Fond National de la Recherche Scientifique (FNRS, grants J010615F and 29127680). Acknowledgments
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