The methods to obtain chitooligosaccharides are tightly related to the physicochemical properties of the end products. Knowledge of these physicochemical characteristics is crucial to describing the biological functions of chitooligosaccharides. Chitooligosaccharides were prepared either in a single-step enzymatic hydrolysis using chitosanase, or in a two-step chemical-enzymatic hydrolysis. The hydrolyzed products obtained in the single-step preparation were composed mainly of 42% fully deacetylated oligomers plus 54% monoacetylated oligomers, and they attenuated the inflammation in lipopolysaccharide-induced mice and in RAW264.7 macrophages. However, chitooligosaccharides from the two-step preparation were composed of 50% fully deacetylated oligomers plus 27% monoacetylated oligomers and, conversely, they promoted the inflammatory response in both in vivo and in vitro models. Similar proportions of monoacetylated and deacetylated oligomers is necessary for the mixtures of chitooligosaccharides to achieve anti-inflammatory effects, and it directly depends on the preparation method to which chitosan was submitted.

The modulation of the host’s metabolism to protect tissue from damage induces tolerance to infections increasing survival. Here, we examined the role of the thyroid hormones, key metabolic regulators, in the outcome of malaria. Hypothyroidism confers protection to experimental cerebral malaria by a disease tolerance mechanism. Hypothyroid mice display increased survival after infection with Plasmodium berghei ANKA, diminishing intracranial pressure and brain damage, without altering pathogen burden, blood-brain barrier disruption, or immune cell infiltration. This protection is reversed by treatment with a Sirtuin 1 inhibitor, while treatment of euthyroid mice with a Sirtuin 1 activator induces tolerance and reduces intracranial pressure and lethality. This indicates that thyroid hormones and Sirtuin 1 are previously unknown targets for cerebral malaria treatment, a major killer of children in endemic malaria areas.

Bone marrow erythropoiesis is mainly homeostatic and a demand of oxygen in tissues activates stress erythropoiesis in the spleen. Here, we show an increase in the number of circulating erythrocytes in apolipoprotein E^−/− mice fed a Western high-fat diet, with similar number of circulating leukocytes and CD41⁺ events (platelets). Atherogenic conditions increase spleen erythropoiesis with no variations of this cell lineage in the bone marrow. Spleens from atherogenic mice show augmented number of late-stage erythroblasts and biased differentiation of progenitor cells towards the erythroid cell lineage, with an increase of CD71⁺CD41CD34⁻CD117⁺Sca1⁻Lin⁻ cells (erythroid-primed megakaryocyte-erythroid progenitors), which is consistent with the way in which atherogenesis modifies the expression of pro-erythroid and pro-megakaryocytic genes in megakaryocyte-erythroid progenitors. These data explain the transiently improved response to an acute severe hemolytic anemia insult found in atherogenic mice in comparison to control mice, as well as the higher burst-forming unit-erythroid and colony forming unit-erythroid capacity of splenocytes from atherogenic mice. In conclusion, our work demonstrates that, along with the well stablished enhancement of monocytosis during atherogenesis, stress erythropoiesis in apolipoprotein E^−/− mice fed a Western high fat diet results in increased numbers of circulating red blood cells.