Unexpected human cases of cutaneous anthrax in Latium region, Italy, August 2017: integrated human–animal investigation of epidemiological, clinical, microbiological and ecological factors

On 31 August, a veterinarian and a farmworker were hospitalised for skin lesions. Both had been exposed to a dead cow on 19 August on a farm near Rome, where eight further cattle died of confirmed anthrax later the same month. At admission, the first case showed a black depressed eschar and another smaller lesion on one hand. The second case presented deep infection of the skin, with involvement of both arms. Anthrax diagnosis was confirmed by detection of B. anthracis DNA in eschar fragments from both patients. T-cell specific immunity was studied by flow cytometry and Elispot assay after stimulation with B. anthracis secretome in blood samples collected from Case 1. Immunoglobulin production was detected by complement fixation assay. In Case 1, specific CD4+ T-cell activation was detected, without antibody production. Specific antibodies were detected only in the second patient with severe cutaneous illness. Both patients recovered. The two human anthrax cases were epidemiologically linked, but anthrax was not suspected at admission in either case. The veterinarian had initially unrecognised professional exposure and the exposed farmworker did initially not report exposure to affected animals. A One Health strategy integrating human and animal investigations was essential to confirm the diagnosis.

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Combination Treatment of Topical Imiquimod Plus Anti-PD-1 Antibody Exerts Significantly Potent Antitumor Effect

Cancers ◽

10.3390/cancers13163948 ◽

2021 ◽

Vol 13 (16) ◽

pp. 3948

Author(s):

Kazumasa Oya ◽

Yoshiyuki Nakamura ◽

Zhu Zhenjie ◽

Ryota Tanaka ◽

Naoko Okiyama ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Combination Therapy ◽

T Cell Activation ◽

Cd8 T Cells ◽

Cell Activation ◽

Antitumor Effect ◽

Skin Lesions ◽

Ifn Γ ◽

Deficient Mice

The exact mechanisms of the imiquimod (IMQ)-induced antitumor effect have not been fully understood. Although both topical IMQ treatment and anti-PD-1 antibody may be used for primary skin lesions or skin metastases of various cancers, the efficacy of each monotherapy for these lesions is insufficient. Using a murine tumor model and human samples, we aimed to elucidate the detailed mechanisms of the IMQ-induced antitumor effect and analyzed the antitumor effect of combination therapy of topical IMQ plus anti-PD-1 antibody. Topical IMQ significantly suppressed the tumor growth of MC38 in wildtype mice. IMQ upregulated interferon γ (IFN-γ) expression in CD8+ T cells in both the lymph nodes and the tumor, and the antitumor effect was abolished in both Rag1-deficient mice and IFN-γ-deficient mice, indicating that IFN-γ produced by CD8+ T cells play a crucial role in the IMQ-induced antitumor effect. IMQ also upregulated PD-1 expression in T cells as well as PD-L1/PD-L2 expression in myeloid cells, suggesting that IMQ induces not only T-cell activation but also T-cell exhaustion by enhanced PD-1 inhibitory signaling. Combination therapy of topical IMQ plus anti-PD-1 antibody exerted a significantly potent antitumor effect when compared with each single therapy, indicating that the combination therapy is a promising therapy for the skin lesions of various cancers.

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Late Onset Ipilimumab-Induced Pericarditis and Pericardial Effusion: A Rare but Life Threatening Complication

Case Reports in Oncological Medicine ◽

10.1155/2015/794842 ◽

2015 ◽

Vol 2015 ◽

pp. 1-5 ◽

Cited By ~ 14

Author(s):

Seongseok Yun ◽

Nicole D. Vincelette ◽

Iyad Mansour ◽

Dana Hariri ◽

Sara Motamed

Keyword(s):

T Cell ◽

T Cell Activation ◽

Cutaneous Melanoma ◽

Cell Activation ◽

Cytotoxic T Lymphocyte ◽

Late Onset ◽

Human Monoclonal Antibody ◽

Phase Iii ◽

First Case ◽

Immune Mediated

Metastatic cutaneous melanoma has poor prognosis with 2-year survival rate of 10–20%. Melanoma cells express various antigens including gp100, melanoma antigen recognized by T cells 1 (MART-1), and tyrosinase, which can induce immune-mediated anticancer response via T cell activation. Cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) is an immune check point molecule that negatively regulates T cell activation and proliferation. Accordingly, recent phase III clinical trials demonstrated significant survival benefit with ipilimumab, a human monoclonal antibody (IgG1) that blocks the interaction of CTLA-4 with its ligands. Since the efficacy of ipilimumab depends on T cell activation, it is associated with substantial risk of immune mediated adverse reactions such as colitis, hepatitis, thyroiditis, and hypophysitis. We report the first case of late onset pericarditis and cardiac tamponade associated with ipilimumab treatment in patient with metastatic cutaneous melanoma.

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IL-33 expression in response to SARS-CoV-2 correlates with seropositivity in COVID-19 convalescent individuals

10.1101/2020.07.09.20148056 ◽

2020 ◽

Author(s):

Michal A Stanczak ◽

David E Sanin ◽

Petya Apostolova ◽

Gabriele Nerz ◽

Dimitrios Lampaki ◽

...

Keyword(s):

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Bronchoalveolar Lavage Fluid ◽

Lavage Fluid ◽

Mediated Effects ◽

Household Transmission ◽

Professional Exposure ◽

Previous Infection ◽

Peptide Stimulation

Our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still developing. We investigated seroprevalence and immune responses in subjects professionally exposed to SARS-CoV-2 and their family members (155 individuals; ages 5-79 years). Seropositivity for SARS-CoV-2 spike glycoprotein aligned with PCR results that confirmed previous infection. Anti-spike IgG titers remained high 60 days post-infection and did not associate with symptoms, but spike-specific IgM did associate with malaise and fever. We found limited household transmission, with children of infected individuals seldomly seropositive, highlighting professional exposure as the dominant route of infection in our cohort. We analyzed PBMCs from a subset of seropositive and seronegative adults. TLR7 agonist- activation revealed an increased population of IL-6+TNF-IL-1β+ monocytes, while SARS-CoV-2 peptide stimulation elicited IL-33, IL-6, IFNa2, and IL-23 expression in seropositive individuals. IL-33 correlated with CD4+ T cell activation in PBMCs from convalescent subjects, and was likely due to T cell-mediated effects on IL-33- producing cells. IL-33 is associated with pulmonary infection and chronic diseases like asthma and COPD, but its role in COVID-19 is unknown. Analysis of published scRNAseq data of bronchoalveolar lavage fluid (BALF) from patients with mild to severe COVID-19 revealed a population of IL-33-producing cells that increases with disease. Together these findings show that IL-33 production is linked to SARS-CoV- 2 infection and warrant further investigation of IL-33 in COVID-19 pathogenesis and immunity.

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