Corrigendum: Bacillus Calmette-Guérin-Induced Trained Immunity Is Not Protective for Experimental Influenza A/Anhui/1/2013 (H7N9) Infection in Mice.

[This corrects the article DOI: 10.3389/fimmu.2018.

Bacillus Calmette-Guérin-Induced Trained Immunity Is Not Protective for Experimental Influenza A/Anhui/1/2013 (H7N9) Infection in Mice.

Avian influenza A of the subtype H7N9 has been responsible for almost 1,600 confirmed human infections and more than 600 deaths since its first outbreak in 2013. Although sustained human-to-human transmission has not been reported yet, further adaptations to humans in the viral genome could potentially lead to an influenza pandemic, which may have severe consequences due to the absence of pre-existent immunity to this strain at population level. Currently there is no influenza A (H7N9) vaccine available.

TGF-β inhibitor Smad7 regulates dendritic cell-induced autoimmunity.

TGF-β is an anti-inflammatory cytokine whose signaling is negatively controlled by Smad7. Previously, we established a role for Smad7 in the generation of autoreactive T cells; however, the function of Smad7 in dendritic cells (DCs) remains elusive. Here, we demonstrate that DC-specific Smad7 deficiency resulted in elevated expression of the transcription factors Batf3 and IRF8, leading to increased frequencies of CD8CD103 DCs in the spleen.

IL-10 control of CD11c+ myeloid cells is essential to maintain immune homeostasis in the small and large intestine.

Although IL-10 promotes a regulatory phenotype of CD11c+ dendritic cells and macrophages in vitro, the role of IL-10 signaling in CD11c+ cells to maintain intestinal tolerance in vivo remains elusive. To this aim, we generated mice with a CD11c-specific deletion of the IL-10 receptor alpha (Cd11ccreIl10rafl/fl). In contrast to the colon, the small intestine of Cd11ccreIl10rafl/fl mice exhibited spontaneous crypt hyperplasia, increased numbers of intraepithelial lymphocytes and lamina propria T cells, associated with elevated levels of T cell-derived IFNγ and IL-17A.

Conditional deletion of TGF-βR1 using Langerin-Cre mice results in Langerhans cell deficiency and reduced contact hypersensitivity.

The critical role of Langerhans cells (LC) in contact hypersensitivity (CHS) was recently questioned in studies using different LC-depletion mouse models. On one hand, inducible ablation of LC led to diminished ear swelling, suggesting functional redundancy between LC and (Langerin(+)) dermal dendritic cells (DC). On the other hand, constitutive or acute depletion of LC resulted in an enhanced reaction, supporting a regulatory role of LC in CHS.

IL-10 controls dendritic cell-induced T-cell reactivation in the skin to limit contact hypersensitivity.

Background: IL-10 is a pleiotropic cytokine and potent negative regulator of both innate and adaptive immune responses. Consequently, IL-10-deficient (IL-10(-/-)) mice have enhanced contact hypersensitivity (CHS) to topical hapten.

Objective: Although the importance of IL-10 production by (regulatory) T cells and Langerhans cells in regulating CHS has been established by cell type-specific il-10 gene targeting, it remains elusive to what extent IL-10 controls dendritic cell (DC) function in vivo.

TGF-beta is required to maintain the pool of immature Langerhans cells in the epidermis.

The pivotal role of TGF-beta in Langerhans cell (LC) development has been previously established in TGF-beta-deficient mice, which lack epidermal LCs. As to whether TGF-beta also governs LC homeostasis and function remains elusive. To assess the role of TGF-beta-mediated control of cutaneous dendritic cells (DCs) in vivo, we generated mice with a conditional knockout of the TGF-beta receptor 1 (TbetaR1) under a DC-specific promoter (DC-TbetaR1(del) mice).

Langerhans cells: critical regulators of skin immunity?

Langerhans cells (LC) are members of the heterogenous family of professional antigen presenting dendritic cells (DC). They are identified by the C-type lectin receptor Langerin and form a contiguous network in the epidermis. Consequently, LC are an integral part of the skin barrier to the environment and were considered to be critical inducers of skin immunity, whereas dermal DC were largely overlooked.

Mannosylated self-peptide inhibits the development of experimental autoimmune encephalomyelitis via expansion of nonencephalitogenic T cells.

Tolerance to experimental autoimmune encephalomyelitis (EAE) in SJL mice can be induced by immunization with a mannosylated form of the proteolipid protein (M-PLP139-151), despite the presence of CFA. The state of tolerance is characterized by poor delayed-type hypersensitivity responses and the absence of clinical EAE symptoms. In vivo monitoring of CFSE-labeled PLP139-151-specific TCR-transgenic (5B6) T cells revealed that immunization with M-PLP139-151 increases the clonal expansion of 5B6 T cells that do not develop full effector functions.

Immunization with mannosylated peptide induces poor T cell effector functions despite enhanced antigen presentation.

In this study, we investigated the development of T cell responses in mice after administration of a mannosylated ovalbumin peptide (M-OVA(323-339)). Immunization with M-OVA(323-339) in complete adjuvant resulted in enhanced antigen presentation in draining lymph nodes. Monitoring the fate of CFSE-labeled ovalbumin peptide-specific TCR transgenic CD4(+) T cells revealed that immunization with M-OVA(323-339) induced normal clonal expansion, recirculation and CD62L expression of antigen-specific T cells in vivo.

Soluble mannosylated myelin peptide inhibits the encephalitogenicity of autoreactive T cells during experimental autoimmune encephalomyelitis.

We have previously shown that immunization with a mannosylated myelin peptide in complete adjuvant induces tolerance instead of disease in experimental autoimmune encephalomyelitis (EAE), a rodent model for multiple sclerosis. In this report we demonstrate that treatment with a soluble mannosylated epitope of proteolipid protein (M-PLP(139-151)) significantly inhibits disease mediated by autoreactive myelin-specific T cells during EAE. Treatment with M-PLP(139-151), applied in different EAE models, significantly reduced the incidence of disease and the severity of clinical symptoms.

Mannosylated PLP(139-151) induces peptide-specific tolerance to experimental autoimmune encephalomyelitis.

SJL mice immunized with mannosylated (M-) PLP(139-151) in complete adjuvant do not develop EAE and little CNS mononuclear cell infiltration; other mannosylated peptides were ineffective in this experimental setting. Despite apparently normal T cell responses, M-PLP(139-151)-immunized mice show impaired delayed-type-sensitivity to PLP(139-151) but a normal response to other peptides. After re-immunization with PLP(139-151) in complete adjuvant, these mice are largely tolerant to EAE, show less T cell proliferation and decreased peptide-specific IgG2a.