Control of immunopathology during Plasmodium infection by hepcidin.

Malaria is a major health problem affecting millions of people annually especially in underdeveloped countries. Mutations causing alterations in hemoglobin production or structure are known to afford protection against the development of severe forms of malaria. Not surprinsingly, these hemoglobin disorders are present at high frequency in areas where malaria is endemic, indicating a survival advantage for individuals carrying them.

Sickle hemoglobin confers tolerance to Plasmodium infection.

Sickle human hemoglobin (Hb) confers a survival advantage to individuals living in endemic areas of malaria, the disease caused by Plasmodium infection. As demonstrated hereby, mice expressing sickle Hb do not succumb to experimental cerebral malaria (ECM). This protective effect is exerted irrespectively of parasite load, revealing that sickle Hb confers host tolerance to Plasmodium infection.

A central role for free heme in the pathogenesis of severe sepsis.

Low-grade polymicrobial infection induced by cecal ligation and puncture is lethal in heme oxygenase-1-deficient mice (Hmox1(-/-)), but not in wild-type (Hmox1(+/+)) mice. Here we demonstrate that the protective effect of this heme-catabolizing enzyme relies on its ability to prevent tissue damage caused by the circulating free heme released from hemoglobin during infection. Heme administration after low-grade infection in mice promoted tissue damage and severe sepsis.

Bariatric surgery reverses natural killer (NK) cell activity and NK-related cytokine synthesis impairment induced by morbid obesity.

Background: Obesity is related to a higher rate of infections and some types of cancer. Here we analyzed the impact of obesity and weight loss induced by Roux-en-Y gastric bypass (RYGB) on immunological parameters, i.e.

Immunoregulatory effects of HO-1: how does it work?

The heme-catabolizing enzyme heme oxygenase-1 (HO-1; encoded by the Hmox1 gene) inhibits the pathogenesis of several immune-mediated inflammatory diseases. This unusually broad salutary effect is thought to rely on the immunoregulatory actions of HO-1, exerted on innate and adaptive immune cells. According to this notion, HO-1 'dampens' innate and adaptive immune responses, limiting immune-mediated tissue injury and thus suppressing the pathogenesis of immune-mediated inflammatory diseases.

Impact of adiposity on immunological parameters.

Studies evaluating immune function in obese humans and experimental animals indicate that the excess adiposity is associated with impaired in immune responses. Obesity is related to a higher rate of infections and to some types of cancer. Nutritional, metabolic and endocrine factors are implicated in the immunological changes.

Expansion of CD4+ CD25+ Foxp3+ T cells by bone marrow-derived dendritic cells.

Dendritic cells (DCs) are the most important antigen-presenting cells of the immune system and have a crucial role in T-lymphocyte activation and adaptive immunity initiation. However, DCs have also been implicated in maintaining immunological tolerance. In this study, we evaluated changes in the CD4(+) CD25(+) Foxp3(+) T-cell population after co-culture of lymph node cells from BALB/c mice with syngeneic bone marrow-derived DCs.

Donor bone marrow cells play a role in the prevention of accelerated graft rejection induced by semi-allogeneic spleen cells in transplantation.

Spleen or spleen plus bone marrow cells from (BALB/cxC57Bl/6)F1 donors were transferred into BALB/c recipients 21 days before skin or cardiac transplantation. Prolonged graft survival was observed on recipients treated with the mixture of donor-derived cells as compared to those treated with spleen cells alone. We evaluated the expression of CD45RB and CD44 by splenic CD4+ and CD8+ T cells 7 and 21 days after donor cell transfer.