Indoleamine 2,3-dioxygenase 1 signaling orchestrates immune tolerance in -infected mice.

The cestode larva infection causes lethal zoonotic alveolar echinococcosis (AE), a disease posing a great threat to the public health worldwide. This persistent hepatic tumor-like disease in AE patients has been largely attributed to aberrant T cell responses, of which Th1 responses are impeded, whilst Th2 and regulatory T cell responses are elevated, creating an immune tolerogenic microenvironment in the liver. However, the immune tolerance mechanisms are not fully understood.

IL-27 Signaling Promotes Th1 Responses and Is Required to Inhibit Fungal Growth in the Lung during Repeated Exposure to .

is an opportunistic fungal pathogen that causes a wide spectrum of diseases in humans, including life-threatening invasive infections as well as several hypersensitivity respiratory disorders. Disease prevention is predicated on the host's ability to clear from the lung while also limiting inflammation and preventing allergic responses. IL-27 is an important immunoregulatory cytokine, but its role during infection remains poorly understood.

CXCR6+CD4+ T cells promote mortality during Trypanosoma brucei infection.

Liver macrophages internalize circulating bloodborne parasites. It remains poorly understood how this process affects the fate of the macrophages and T cell responses in the liver. Here, we report that infection by Trypanosoma brucei induced depletion of macrophages in the liver, leading to the repopulation of CXCL16-secreting intrahepatic macrophages, associated with substantial accumulation of CXCR6+CD4+ T cells in the liver.

Quantitative analysis reveals internalisation of Cryptococcus neoformans by brain endothelial cells in vivo.

Migration of Cryptococcus neoformans from the blood to the brain parenchyma is crucial to cause fatal meningoencephalitis. Although mechanisms involved in brain migration of C. neoformans have been widely studied in vitro, less is known about how the fungus crosses the blood-brain barrier (BBB) in vivo.

IL-27 Negatively Regulates Tip-DC Development during Infection.

Tumor necrosis factor (TNF)/inducible nitric oxide synthase (iNOS)-producing dendritic cells (Tip-DCs) have profound impacts on host immune responses during infections. The mechanisms regulating Tip-DC development remain largely unknown. Here, using a mouse model of infection with African trypanosomes, we show that a deficiency in interleukin-27 receptor (IL-27R) signaling results in escalated intrahepatic accumulation of Ly6C-positive (Ly6C) monocytes and their differentiation into Tip-DCs.

VCAM1/VLA4 interaction mediates Ly6Clow monocyte recruitment to the brain in a TNFR signaling dependent manner during fungal infection.

Monocytes exist in two major populations, termed Ly6Chi and Ly6Clow monocytes. Compared to Ly6Chi monocytes, less is known about Ly6Clow monocyte recruitment and mechanisms involved in the recruitment of this subset. Furthermore, the role of Ly6Clow monocytes during infections is largely unknown.

CRIg plays an essential role in intravascular clearance of bloodborne parasites by interacting with complement.

Although CRIg was originally identified as a macrophage receptor for binding complement C3b/iC3b in vitro, recent studies reveal that CRIg functions as a pattern recognition receptor in vivo for Kupffer cells (KCs) to directly bind bacterial pathogens in a complement-independent manner. This raises the critical question of whether CRIg captures circulating pathogens through interactions with complement in vivo under flow conditions. Furthermore, the role of CRIg during parasitic infection is unknown.

Fungal dissemination is limited by liver macrophage filtration of the blood.

Fungal dissemination into the bloodstream is a critical step leading to invasive fungal infections. Here, using intravital imaging, we show that Kupffer cells (KCs) in the liver have a prominent function in the capture of circulating Cryptococcus neoformans and Candida albicans, thereby reducing fungal dissemination to target organs. Complement C3 but not C5, and complement receptor CRIg but not CR3, are involved in capture of C.

Interferon Gamma in African Trypanosome Infections: Friends or Foes?

African trypanosomes cause fatal infections in both humans and livestock. Interferon gamma (IFN-γ) plays an essential role in resistance to African trypanosomes. However, increasing evidence suggests that IFN-γ, when excessively synthesized, also induces immunopathology, enhancing susceptibility to the infection.

Intravascular clearance of disseminating Cryptococcus neoformans in the brain can be improved by enhancing neutrophil recruitment in mice.

Extrapulmonary dissemination of Cryptococcus neoformans (C. neoformans) is one of the most critical steps in the development of meningoencephalitis. Here, we report that clearance of the disseminating C.

Real-Time Imaging of Interactions of Neutrophils with Cryptococcus neoformans Demonstrates a Crucial Role of Complement C5a-C5aR Signaling.

Neutrophils have been shown to efficiently kill Cryptococcus neoformans, a causative agent of meningoencephalitis. Here, using live-cell imaging, we characterize the dynamic interactions of neutrophils with C. neoformans and the underlying mechanisms in real time.

Real-time in vivo imaging reveals the ability of neutrophils to remove Cryptococcus neoformans directly from the brain vasculature.

Although neutrophils are typically the first immune cells attracted to an infection site, little is known about how neutrophils dynamically interact with invading pathogens in vivo. Here, with the use of intravital microscopy, we demonstrate that neutrophils migrate to the arrested Cryptococcus neoformans, a leading agent to cause meningoencephalitis, in the brain microvasculature. Following interactions with C.

IL-27 Signaling Is Crucial for Survival of Mice Infected with African Trypanosomes via Preventing Lethal Effects of CD4+ T Cells and IFN-γ.

African trypanosomes are extracellular protozoan parasites causing a chronic debilitating disease associated with a persistent inflammatory response. Maintaining the balance of the inflammatory response via downregulation of activation of M1-type myeloid cells was previously shown to be crucial to allow prolonged survival. Here we demonstrate that infection with African trypanosomes of IL-27 receptor-deficient (IL-27R-/-) mice results in severe liver immunopathology and dramatically reduced survival as compared to wild-type mice.

Distinct Contributions of CD4+ and CD8+ T Cells to Pathogenesis of Trypanosoma brucei Infection in the Context of Gamma Interferon and Interleukin-10.

Although gamma interferon (IFN-γ) and interleukin-10 (IL-10) have been shown to be critically involved in the pathogenesis of African trypanosomiasis, the contributions to this disease of CD4(+) and CD8(+) T cells, the major potential producers of the two cytokines, are incompletely understood. Here we show that, in contrast to previous findings, IFN-γ was produced by CD4(+), but not CD8(+), T cells in mice infected with Trypanosoma brucei. Without any impairment in the secretion of IFN-γ, infected CD8(-/-) mice survived significantly longer than infected wild-type mice, suggesting that CD8(+) T cells mediated mortality in an IFN-γ-independent manner.

Acrylamide induces mitochondrial dysfunction and apoptosis in BV-2 microglial cells.

Acrylamide (ACR), a potent neurotoxin, can be produced during food processing at high temperature. This study examined the redox-dependent apoptotic and inflammatory responses of ACR in an immortalized mouse microglia cell line BV2. The exposure of BV2 cells to ACR reduced cell viability and induced apoptosis in a concentration-dependent manner.