Correction: Helminth Colonization Is Associated with Increased Diversity of the Gut Microbiota.

[This corrects the article DOI: 10.1371/journal.pntd.

Vitamin A mediates conversion of monocyte-derived macrophages into tissue-resident macrophages during alternative activation.

It remains unclear whether activated inflammatory macrophages can adopt features of tissue-resident macrophages, or what mechanisms might mediate such a phenotypic conversion. Here we show that vitamin A is required for the phenotypic conversion of interleukin 4 (IL-4)-activated monocyte-derived F4/80CD206PD-L2MHCII macrophages into macrophages with a tissue-resident F4/80CD206PD-L2MHCIIUCP1 phenotype in the peritoneal cavity of mice and during the formation of liver granulomas in mice infected with Schistosoma mansoni. The phenotypic conversion of F4/80CD206 macrophages into F4/80CD206 macrophages was associated with almost complete remodeling of the chromatin landscape, as well as alteration of the transcriptional profiles.

Experimental cerebral malaria pathogenesis--hemodynamics at the blood brain barrier.

Cerebral malaria claims the lives of over 600,000 African children every year. To better understand the pathogenesis of this devastating disease, we compared the cellular dynamics in the cortical microvasculature between two infection models, Plasmodium berghei ANKA (PbA) infected CBA/CaJ mice, which develop experimental cerebral malaria (ECM), and P. yoelii 17XL (PyXL) infected mice, which succumb to malarial hyperparasitemia without neurological impairment.

Ly6C(high) monocytes become alternatively activated macrophages in schistosome granulomas with help from CD4+ cells.

Alternatively activated macrophages (AAM) that accumulate during chronic T helper 2 inflammatory conditions may arise through proliferation of resident macrophages or recruitment of monocyte-derived cells. Liver granulomas that form around eggs of the helminth parasite Schistosoma mansoni require AAM to limit tissue damage. Here, we characterized monocyte and macrophage dynamics in the livers of infected CX3CR1(GFP/+) mice.

Helminth colonization is associated with increased diversity of the gut microbiota.

Soil-transmitted helminths colonize more than 1.5 billion people worldwide, yet little is known about how they interact with bacterial communities in the gut microbiota. Differences in the gut microbiota between individuals living in developed and developing countries may be partly due to the presence of helminths, since they predominantly infect individuals from developing countries, such as the indigenous communities in Malaysia we examine in this work.

Alternatively activated macrophages derived from monocytes and tissue macrophages are phenotypically and functionally distinct.

Macrophages adopt an alternatively activated phenotype (AAMs) when activated by the interleukin-4receptor(R)α. AAMs can be derived either from proliferation of tissue resident macrophages or recruited inflammatory monocytes, but it is not known whether these different sources generate AAMs that are phenotypically and functionally distinct. By transcriptional profiling analysis, we show here that, although both monocyte and tissue-derived AAMs expressed high levels of Arg1, Chi3l3, and Retnla, only monocyte-derived AAMs up-regulated Raldh2 and PD-L2.

Therapeutic helminth infection of macaques with idiopathic chronic diarrhea alters the inflammatory signature and mucosal microbiota of the colon.

Idiopathic chronic diarrhea (ICD) is a leading cause of morbidity amongst rhesus monkeys kept in captivity. Here, we show that exposure of affected animals to the whipworm Trichuris trichiura led to clinical improvement in fecal consistency, accompanied by weight gain, in four out of the five treated monkeys. By flow cytometry analysis of pinch biopsies collected during colonoscopies before and after treatment, we found an induction of a mucosal T(H)2 response following helminth treatment that was associated with a decrease in activated CD4(+) Ki67+ cells.

Upregulation of retinal dehydrogenase 2 in alternatively activated macrophages during retinoid-dependent type-2 immunity to helminth infection in mice.

Although the vitamin A metabolite retinoic acid (RA) plays a critical role in immune function, RA synthesis during infection is poorly understood. Here, we show that retinal dehydrogenases (Raldh), required for the synthesis of RA, are induced during a retinoid-dependent type-2 immune response elicited by Schistosoma mansoni infection, but not during a retinoid-independent anti-viral immune response. Vitamin A deficient mice have a selective defect in T(H)2 responses to S.

Increased disease severity of parasite-infected TLR2-/- mice is correlated with decreased central nervous system inflammation and reduced numbers of cells with alternatively activated macrophage phenotypes in a murine model of neurocysticercosis.

In a murine model for neurocysticercosis (NCC), intracranial inoculation of the helminth parasite Mesocestoides corti induces multiple Toll-like receptors (TLRs), among which TLR2 is upregulated first and to a relatively high extent. Here, we report that TLR2(-/-) mice displayed significantly increased susceptibility to parasite infection accompanied by increased numbers of parasites in the brain parenchyma compared to infection in wild-type (WT) mice. This coincided with an increased display of microglial nodule formations and greater neuropathology than in the WT.

STAT6⁻/⁻ mice exhibit decreased cells with alternatively activated macrophage phenotypes and enhanced disease severity in murine neurocysticercosis.

In this study, using a murine model for neurocysticercosis, macrophage phenotypes and their functions were examined. Mesocestoides corti infection in the central nervous system (CNS) induced expression of markers associated with alternatively activated macrophages (AAMs) and a scarcity of iNOS, a classically activated macrophage marker. The infection in STAT6(-/-) mice resulted in significantly reduced accumulation of AAMs as well as enhanced susceptibility to infection coinciding with increased parasite burden and greater neuropathology.

Mesocestoides corti intracranial infection as a murine model for neurocysticercosis.

Neurocysticercosis (NCC) is the most common parasitic disease of the central nervous system (CNS) caused by the larval form of the tapeworm Taenia solium. NCC has a long asymptomatic period with little or no inflammation, and the sequential progression to symptomatic NCC depends upon the intense inflammation associated with degeneration of larvae. The mechanisms involved in these progressive events are difficult to study in human patients.

MyD88-deficient mice exhibit decreased parasite-induced immune responses but reduced disease severity in a murine model of neurocysticercosis.

The symptomatic phase of neurocysticercosis (NCC), a parasitic disease of the central nervous system (CNS) in humans, is characterized by inflammatory responses leading to neuropathology and, in some cases, death. In an animal model of NCC in which mice were intracranially inoculated with the parasite Mesocestoides corti, the infection in mice lacking the myeloid differentiation primary response gene 88 (MyD88(-/-)) resulted in decreased disease severity and improved survival compared with that in wild-type (WT) mice. The CNS of MyD88(-/-) mice was more quiescent, with decreased microgliosis and tissue damage.

Toll-like receptors in CNS parasitic infections.

Parasite infections in the central nervous system (CNS) are a major cause of morbidity and mortality worldwide, second only to HIV infection. Finding appropriate therapeutic measures to control CNS parasite infections requires an understanding of the tissue-specific host response. CNS parasitic diseases are invariably associated with persistent T-helper 1 (Th1) cytokine-dependent proinflammatory responses.

Expression and distribution of Toll-like receptors 11-13 in the brain during murine neurocysticercosis.

The functions of Toll-like receptors (TLRs) 11-13 in central nervous system (CNS) infections are currently unknown. Using a murine model of neurocysticercosis, we investigated the expression and distribution of TLRs 11-13 by using both gene specific real-time PCR analysis and in situ immunofluorescence microscopy in both control and neurocysticercosis brains. In the mock infected brain, mRNAs of TLRs 11-13 were constitutively expressed.