Extrafollicular Plasmablasts Present in the Acute Phase of Infections Express High Levels of PD-L1 and Are Able to Limit T Cell Response.

During infections with protozoan parasites or some viruses, T cell immunosuppression is generated simultaneously with a high B cell activation. It has been described that, as well as producing antibodies, plasmablasts, the differentiation product of activated B cells, can condition the development of protective immunity in infections. Here, we show that, in T. cruzi infection, all the plasmablasts detected during the acute phase of the infection had higher surface expression of PD-L1 than other mononuclear cells. PD-L1hi plasmablasts were induced in vivo in a BCR-specific manner and required help from Bcl-6+CD4+T cells. PD-L1hi expression was not a characteristic of all antibody-secreting cells since plasma cells found during the chronic phase of infection expressed PD-L1 but at lower levels. PD-L1hi plasmablasts were also present in mice infected with Plasmodium or with lymphocytic choriomeningitis virus, but not in mice with autoimmune disorders or immunized with T cell-dependent antigens. In vitro experiments showed that PD-L1hi plasmablasts suppressed the T cell response, partially via PD-L1. Thus, this study reveals that extrafollicular PD-L1hi plasmablasts, whose peaks of response precede the peak of germinal center response, may have a modulatory function in infections, thus influencing T cell response.

Role of Mus musculus in the transmission of several pathogens in poultry farms.

This study aimed to analyze the role of Mus musculus as a host of Leptospira spp., lymphocytic choriomeningitis virus (LCMV) and Toxoplasma gondii, in poultry farms of Buenos Aires province, Argentina, and to assess the potential risk of transmission to humans and domestic or breeding animals. Samplings were performed between 2009 and 2011 (S1) and during 2016 (S2). In S1, we studied the prevalence of infection for Leptospira spp. and LCMV, whereas, in S2, we studied the prevalence of infection for Leptospira spp. and T. gondii. In S1, we found an overall Leptospira spp. prevalence in M. musculus of 18% (14/79) and no positive serum samples for LCMV (0/166). In S2, we detected no positive individuals for Leptospira spp. (0/56) and an overall T. gondii seroprevalence of 3.6% (2/56). The probability of Leptospira spp. infection in M. musculus was higher in reproductively active individuals and in samplings subsequent to months with high accumulated precipitation. Our results suggest that, in the poultry farms studied, the presence of M. musculus may be a risk factor in the transmission of Leptospira spp. and T. gondii to humans and domestic animals. The management of farms should include biosecurity measures for farm workers and more effective rodent control.

Late cytomegalovirus (CMV) infections after kidney transplantation under the preemptive strategy: Risk factors and clinical aspects.

BACKGROUND: Late cytomegalovirus infections (LCMV) after the cessation of prophylaxis are well described. We aimed to assess clinical and epidemiological data on late-occurring cytomegalovirus (CMV) infections in the absence of CMV prophylaxis in a cohort of kidney transplant patients. METHODS: In a cohort of kidney transplant recipients not employing CMV-specific prophylaxis, patients with CMV infections occurring after 6 months of transplantation were compared to patients with CMV infections diagnosed within the first 6 months (early infections). The main objectives were to compare clinical outcomes and evaluate risk factors for late CMV infection. RESULTS: A total of 556 patients were evaluated. Forty-three patients with LCMV infections were compared to 513 patients with early CMV infections. LCMV infections occurred after a median of 473 days of transplantation and had a more severe course, with a statistically significant higher rate of invasive disease and graft loss (60.5% vs 21.6% and 11.6% vs 3.1% respectively). Thirty-day mortality was twice as high for patients with LCMV, but did not reach statistical significance (9.3% vs 4.3%). By multivariate analysis, employment of antilymphocyte therapy early after transplantation and tacrolimus as initial immunosuppressive therapy were significantly protective for the occurrence of LCMV infections. CONCLUSION: Late CMV infections in the absence of specific prophylaxis after kidney transplantation have a more severe outcome when compared to early infections and occur in patients less immunosuppressed early after transplantation.

Contribution of the murine and primate models to thestudy of arenaviral diseases and hemorrhagic fevers / Contribución de los modelos murino y primate al estudio de las enfermedades porarenavirus y fiebres hemorrágicas / Contribuição dos modelos murinos e primatas ao estudo de doenças por arenavirus efebre hemorrágica

This manuscript is an inedited part of my PhD dissertation, based on historical and recent findingson animal models, that was presented as part of the requirements to fulfill the conditions to become aphilosophical doctor on Veterinary Sciences at the University of Wisconsin on October of 2003.The currentmini-review written on a free-version style, underlines some of the cornerstones of immunology as ascience, understood thanks to the use of the Lymphocytic Choriomeningitis virus (LCMV) experimentallyand naturally infected mouse model. It should suffice to say that there have been two Nobel prices ofMedicine for discoveries made through the employment of this animal model, in order to recognize theright importance to it. In addition, several laboratories, Dr. Salvato´s among them, have also employed theLCMV-infected Rhesus monkey model as a tool to unravel the mysteries of arenaviral hemorrhagic fever,and particularly the physiopathology of Lassa disease in humans. Here I show some of the knowledgegenerated through the study of both animal infections.

El siguiente manuscrito, es un capítulo inédito de mi tesis doctoral, basado en hallazgos históricos yrecientes sobre modelos animales, que fue presentado como parte de los requisitos para obtener el títulode Ph.D. en Ciencias veterinarias en la Universidad de Wisconsin, en Octubre de 2003.La actual minirevisiónescrita en estilo de versión libre, subraya algunas de las piedras angulares de la inmunología comociencia, entendidas gracias al uso del modelo murino infectado natural y experimentalmente con el virusde Coriomeningitis Linfocítica (LCMV). Sería suficiente mencionar que han existido dos premios Nóbelde Medicina por descubrimientos realizados a través del empleo de este modelo animal, para reconocer lareal importancia del mismo. Adicionalmente, varios laboratorios, el de la Dra. Salvato entre ellos, tambiénhan empleado el modelo del mono Rhesus como un instrumento para desvelar los misterios de las fiebreshemorrágicas por arenavirus, y particularmente la fisiopatología de la enfermedad de Lassa en humanos.Aquí yo muestro alo del conocimiento generado a través del estudio de ambas infecciones animales.

O seguinte manuscrito é um capítulo inédito da minha tese doutoral, baseado em casos históricose recentes sobre modelos animais, que foram apresentados na defesa da tese de Ph.D. em CiênciasVeterinárias da Universidade de Wisconsin, em outubro de 2003. A atual mini revisão escrita em estilode versão livre, enfatiza em algumas pedras angulares da inmunologìa como ciência. Graças ao usodo modelo murino infectado natural e experimentalmente com o vírus da Coriomeningitis Linfocítica(LCMV). Seria suficiente mencionar que foram outorgados dois prêmios Nobel de Medicina pelosdescobrimentos realizados a través do uso deste modelo, para reconhecer a real importância do mesmo.Adicionalmente, vários laboratórios, entre eles o da Dra. Salvato, tem utilizado o modelo macaco Rhesuscomo um instrumento para desvelar os mistérios das febres hemorrágicas por arenavirus, e particularmentea fisiologia e patologia da doença de Lassa em humanos. Aqui eu indico algo do conhecimento gerado através do estudo das duas infecções animais.

Circulating natural killer and γδ T cells decrease soon after infection of rhesus macaques with lymphocytic choriomeningitis virus

Rhesus macaques infected with the WE strain of lymphocytic choriomeningitis virus (LCMV-WE) serve as a model for human infection with Lassa fever virus. To identify the earliest events of acute infection, rhesus macaques were monitored immediately after lethal infection for changes in peripheral blood mononuclear cells (PBMCs). Changes in CD3, CD4, CD8 and CD20 subsets did not vary outside the normal fluctuations of these blood cell populations; however, natural killer (NK) and γδ T cells increased slightly on day 1 and then decreased significantly after two days. The NK subsets responsible for the decrease were primarily CD3-CD8+ or CD3-CD16+ and not the NKT (primarily CD3+CD56+) subset. Macaques infected with a non-virulent arenavirus, LCMV-Armstrong, showed a similar drop in circulating NK and γδ T cells, indicating that this is not a pathogenic event. V³9 T cells, representing the majority of circulating γδ T cells in rhesus macaques, displayed significant apoptosis when incubated with LCMV in cell culture; however, the low amount of cell death for virus-co-cultured NK cells was insufficient to account for the observed disappearance of this subset. Our observations in primates are similar to those seen in LCMV-infected mice, where decreased circulating NK cells were attributed to margination and cell death. Thus, the disappearance of these cells during acute hemorrhagic fever in rhesus macaques may be a cytokine-induced lymphopenia common to many virus infections.