INVESTIGADORES
GIAMBARTOLOMEI Guillermo Hernan
artículos
Título:
Caveolin-mediated endocytosis of the Chlamydia m278 outer membrane peptide encapsulated in poly (lactic acid)-poly (ethylene glycol) nanoparticles by mouse primary dendritic cells enhances specific immune effectors mediated by MHC class II and CD4+ Tcells
Autor/es:
SAURABH DIXIT; RICHA VERMA; SKYLA DUNCAN; GUILLERMO H. GIAMBARTOLOMEI; SHREE. R. SINGH; DENNIS, VIDA A.
Revista:
BIOMATERIALS
Editorial:
ELSEVIER SCI LTD
Referencias:
Lugar: Amsterdam; Año: 2018
ISSN:
0142-9612
Resumen:
We previously developed a Chlamydia trachomatis nanovaccine (PPM) by encapsulating a chlamydialM278 peptide within poly(lactic acid)-poly(ethylene glycol) biodegradable nanoparticles that immunopotentiatedChlamydia-specific immune effector responses in mice. Herein, we investigated the mechanisticinteractions of PPM with mouse bone marrow-derived dendritic cells (DCs) for its uptake,trafficking, and T cell activation. Our results reveal that PPM triggered enhanced expression of effectorcytokines and chemokines, surface activation markers (Cd1d2, Fcgr1), pathogen-sensing receptors (TLR2,Nod1), co-stimulatory (CD40, CD80, CD86) and MHC class I and II molecules. Co-culturing of PPM-primedDCs with T cells from C. muridarum vaccinated mice yielded an increase in Chlamydia-specific immuneeffector responses including CD3þ lymphoproliferation, CD3þCD4þ IFN-g-secreting cells along withCD3þCD4þ memory (CD44high and CD62Lhigh) and effector (CD44high and CD62Llow) phenotypes. Intracellulartrafficking analyses revealed an intense expression and colocalization of PPM predominantly inendosomes. PPM also upregulated the transcriptional and protein expression of the endocytic mediator,caveolin-1 in DCs. More importantly, the specific inhibition of caveolin-1 led to decreased expression ofPPM-induced cytokines and co-stimulatory molecules. Our investigation shows that PPM providedenhancement of uptake, probably by exploiting the caveolin-mediated endocytosis pathway, endosomalprocessing, and MHC II presentation to immunopotentiate Chlamydia-specific immune effector responsesmediated by CD4þ T cells.