Background: Malaria parasites detoxify copious amounts of heme during human infection, but enzyme involvement remains unclear.Results: Parasite-infected and uninfected erythrocytes contain indistinguishable low levels of heme catabolites, and a heme oxygenase-like parasite protein binds but does not degrade heme.Conclusion:
P. falciparum parasites do not enzymatically degrade heme.Significance: This study comprehensively answers a long standing question regarding heme metabolism in this important parasite.
T cell responses to symbionts in the intestine drive tolerance or inflammation depending on the genetic background of the host. These symbionts in the gut sense the available nutrients and adapt their metabolic programs to utilize these nutrients efficiently. Here, we ask whether diet can alter the expression of a bacterial antigen to modulate adaptive immune responses. We generated a CD4+ T cell hybridoma, BθOM, specific for Bacteroides thetaiotaomicron (B. theta). Adoptively transferred transgenic T cells expressing the BθOM TCR proliferated in the colon, colon-draining lymph node, and spleen in B. theta colonized healthy mice and differentiated into regulatory T (Treg) and effector T (Teff) cells. Depletion of B. theta-specific Tregs resulted in colitis, showing that a single protein expressed by B. theta can drive differentiation of Tregs that self-regulate Teffs to prevent disease. We found that BθOM T cells recognized a peptide derived from a single B. theta protein, BT4295, whose expression is regulated by nutrients, with glucose being a strong catabolite repressor. Mice fed a high glucose diet had a greatly reduced activation of BθOM T cells in the colon. These studies establish that the immune response to specific bacterial antigens can be modified by changes in the diet by altering antigen expression in the microbe.
With modern therapy, overall survival (OS) for children with acute lymphoblastic leukemia approaches 90%. However, inferior outcomes for minority children have been reported. Data on the effects of ethnicity/race as it relates to socioeconomic status are limited. Using state cancer registry data from Texas and Florida, we evaluated the impact of neighborhood-level poverty rate and race/ethnicity on OS for 4719 children with acute lymphoblastic leukemia. On multivariable analysis, patients residing in neighborhoods with the highest poverty rate had a 1.8-fold increase in mortality compared with patients residing in neighborhoods with the lowest poverty rate (hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.41-2.30). Hispanic and non-Hispanic black patients also had increased risk of mortality compared with non-Hispanic white patients (Hispanic: HR, 1.18; 95% CI, 1.01-1.39; non-Hispanic black: HR, 1.31; 95% CI, 1.03-1.66). On subgroup analysis, there was a 21.7% difference in 5-year OS when comparing non-Hispanic white children living in the lowest poverty neighborhoods (5-year OS, 91.2%; 95% CI, 88.6-93.2) to non-Hispanic black children living in the highest poverty neighborhoods (5-year OS, 69.5%; 95% CI, 61.5-76.1). To address such disparities in survival, further work is needed to identify barriers to cancer care in this pediatric population.
This information is current as Antigen in the Intestine Modulate Immune Responses to a Dominant to Bacteroides thetaiotaomicron Symbiont Polysaccharide Capsules Equip the Human
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