In chronic viral infections, suppressed CD8+ T cell responses have been attributed to PD-1:PD-L1

interactions [20]. To the best of our knowledge, we here describe for the first time that SCH727965 datasheet suppressor receptor PD-1 is induced after vaccination with elevated doses of Leishmania LPG or with the infection with elevated amounts of L. mexicana promastigotes. This expression is specifically dominant on CD8+ T lymphocytes possibly leading to a suppression of these cells that are critical in the control of leishmaniasis, both through IFN-γ production, as well as in their cytotoxic effect against autologous Leishmania-infected macrophages [5] and [6]. These results call for a careful pre-immunization evaluation of potential vaccination candidates against Leishmania, since ZD1839 molecular weight the induction of a suppressive effect can lead to detrimental blockage of the immune response, favoring a more virulent disease progression. These data open a new field of research in vaccine developments and provide a novel strategy for therapeutic intervention in leishmaniasis, where the blockade of PD-1 could represent a valuable approach

for anti-Leishmania immunotherapy. Our data also yield information on novel parasite evasion strategies, achieving CD8+ T cell suppression, thereby eliminating one of the more powerful defense mechanisms against L. mexicana [13]. We conclude that vaccination models should assess whether PD-1 and/or PD-L2 are induced, that, far from activating CD8+ T cells, it could lead to their inhibition. Additionally, during experimental models of L. mexicana infections, the parasite load must be taken into account, since it can have opposing effects on PD-1 expression in lymphocytes. This study provides insight into the regulatory pathways elicited

in vaccine models using different Vasopressin Receptor antigen concentrations or during Leishmania infections with different parasite loads, showing that the outcome can be polarly opposed, leading to contradictory results. Maria Berenice Martínez Salazar was supported by a PhD fellowship from CONACyT and is a doctoral student of Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México (UNAM). The Project was financed by CONACyT—102155 and PAPIITIN215212 Conflict of interest: The authors state that there is no conflict of interest. “
“Since the elimination of indigenous measles from the United States (US) was documented in 2000, relatively low numbers of cases per year (average of 71 cases, range 37–140) were reported during this decade [1]. However, in 2011 the country experienced a marked increase in measles cases and outbreaks [2] and [3].