ABSTRACT
Treponema pallidum is the pathogen that causes syphilis, a sexually transmitted disease; however, the pathogenic mechanism of this organism remains unclear. Tp92 is the only T. pallidum outer membrane protein that has structural features similar to the outer membrane proteins of other Gram-negative bacteria, but the exact functions of this protein remain unknown. In the present study, we demonstrated that the recombinant Tp92 protein can induce human mononuclear cell death. Tp92 mediated the human monocytic cell line derived from an acute monicytic leukemia patient (THP-1) cell death by recognizing CD14 and/or TLR2 on cell surfaces. After the stimulation of THP-1 cells by the Tp92 protein, Tp92 may induce atypical pyroptosis of THP-1 cells via the pro-caspase-1 pathway. Meanwhile, this protein caused the apoptosis of THP-1 cells via the receptor-interacting protein kinase 1/caspase-8/aspase-3 pathway. Tp92 reduced the number of monocytes among peripheral blood mononuclear cells. Interestingly, further research showed that Tp92 failed to increase the tumour necrosis factor-α, interleukin (IL)-1ß, IL-6, IL-10, IL-18 and monocyte chemotactic protein 1 (MCP)-1 levels but slightly elevated the IL-8 levels via the Nuclear Factor (NF)-κB pathway in THP-1 cells. The data suggest that Tp92 recognizes CD14 and TLR2, transfers the signal to a downstream pathway, and activates NF-κB to mediate the production of IL-8. This mechanism may help T. pallidum escape recognition and elimination by the host innate immune system.
Subject(s)
Antigens, Surface/genetics , Bacterial Proteins/genetics , Interleukin-8/genetics , Lipopolysaccharide Receptors/genetics , Syphilis/microbiology , Toll-Like Receptor 2/genetics , Caspase 1/genetics , Cell Death/genetics , Cell Line, Tumor , Cytokines/genetics , Host-Pathogen Interactions/genetics , Humans , Leukemia, Monocytic, Acute/genetics , Leukemia, Monocytic, Acute/microbiology , Leukemia, Monocytic, Acute/pathology , Leukocytes, Mononuclear/microbiology , Leukocytes, Mononuclear/pathology , NF-kappa B/genetics , Recombinant Proteins/genetics , Signal Transduction/genetics , Syphilis/genetics , Syphilis/pathology , Treponema pallidum/genetics , Treponema pallidum/pathogenicityABSTRACT
Invasive aspergillosis is an important factor in the morbidity and mortality of patients suffering from hematologic disorders treated with chemotherapy. Treatment with amphotericin B is often limited because of toxicity, particularly nephrotoxicity. We describe a case of invasive pulmonary Aspergillus fumigatus infection in acute myeloid leukemia with renal failure due to amphotericin B therapy, which responded to treatment with a new antifungal agent, micafungin. Micafungin appears to be an effective and safe therapy for Aspergillus infections with renal failure due to amphotericin B.
Subject(s)
Amphotericin B/adverse effects , Aspergillosis/drug therapy , Leukemia, Monocytic, Acute/microbiology , Lipoproteins/therapeutic use , Lung Diseases, Fungal/drug therapy , Peptides, Cyclic/therapeutic use , Renal Insufficiency/chemically induced , Aspergillosis/diagnosis , Aspergillosis/etiology , Echinocandins , Humans , Lipopeptides , Lung Diseases, Fungal/diagnosis , Lung Diseases, Fungal/etiology , Male , Micafungin , Middle Aged , Renal Insufficiency/microbiology , Treatment OutcomeABSTRACT
A 63-year-old man with a history of myeloblastic-monocytic leukaemia developed partly suppurating cutaneous nodules on the lower left leg. The nodules proceeded to spread in a linear fashion up the limb, following the line of the lymphatic drainage. Mycological examination of a skin biopsy demonstrated Scedoporium apiospermum. This case highlights the potential for Scedosporium species to act as opportunistic infections in immunosuppressed humans.
Subject(s)
Dermatomycoses/microbiology , Leg Ulcer/microbiology , Leukemia, Monocytic, Acute/complications , Mycetoma/complications , Opportunistic Infections , Pseudallescheria/isolation & purification , Humans , Leukemia, Monocytic, Acute/microbiology , Male , Microbiological Techniques , Middle AgedABSTRACT
We have recently shown that a short course of high-dose interleukin-2 (IL-2) can markedly inhibit the graft-versus-host disease (GVHD)-promoting activity of donor CD4+ T cells. The difficulty in dissociating GVHD-promoting from graft-versus-leukemia (GVL) effects of alloreactive donor T cells currently prevents clinical bone marrow transplantation (BMT) from fulfilling its full potential. To test the capacity of IL-2 treatment to promote such a dissociation, we have developed a new murine transplantable acute myelogenous leukemia model using a class II major histocompatibility complex-positive BALB/c Moloney murine leukemia virus-induced promonocytic leukemia, 2B-4-2. BALB/c mice receiving 2.5 x 10(5) 2B-4-2 cells intravenously 1 week before irradiation and syngeneic BMT died from leukemia within 2 to 4 weeks after BMT. Administration of syngeneic spleen cells and/or a 2.5-day course of IL-2 treatment alone did not inhibit leukemic mortality. In contrast, administration of non-T-cell-depleted fully allogeneic B10 (H-2b) spleen cells and T-cell-depleted B10 marrow led to a significant delay in leukemic mortality in IL-2-treated mice. In these animals GVHD was inhibited by IL-2 treatment. GVL effects were mediated entirely by donor CD4+ and CD8+ T cells. Remarkably, IL-2 administration did not diminish the magnitude of the GVL effect of either T-cell subset. This was surprising, because CD4-mediated GVHD was inhibited in the same animals in which CD4-mediated GVL effects were not reduced by IL-2 treatment. These results suggest a novel mechanism by which GVHD and GVL effects of a single unprimed alloreactive T-cell subset can be dissociated; different CD4 activities promote GVHD and GVL effects, and the former, but not the latter activities are inhibited by treatment with IL-2.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8 Antigens/immunology , Graft vs Host Disease/prevention & control , Interleukin-2/therapeutic use , Leukemia, Monocytic, Acute/immunology , T-Lymphocytes/immunology , Animals , Bone Marrow Transplantation/immunology , Female , Leukemia, Monocytic, Acute/microbiology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Moloney murine leukemia virus , Transplantation ChimeraABSTRACT
The production of tumor necrosis factor alpha (TNF alpha) and IL-1 beta by the monocytic cell line THP-1, productively infected with HIV-1, was investigated using specific RIA and Northern blot analysis. HIV-infected cells, like uninfected cells, did not constitutively produce any detectable amounts of protein or mRNA for TNF alpha or IL-1 beta. After stimulation with LPS or a combination of LPS plus IFN-gamma, TNF alpha and IL-1 beta were detected in tissue culture supernatants and cell lysates and transcripts for both cytokines were seen on Northern blots. No significant difference in production of these two cytokines was observed between uninfected and chronically infected cells. Acutely HIV-infected cells, however, showed phenotypic changes compatible with maturation and an increase in TNF alpha and IL-1 beta mRNA production, and released significantly higher levels of TNF alpha and IL-1 beta compared with chronically infected or uninfected cells. Furthermore, LPS stimulation of HIV-infected cells increased virus production. These results suggest that HIV-infected monocytic cells may produce increased amounts of TNF alpha and IL-1 beta in response to stimuli that could be present in vivo.
Subject(s)
Acquired Immunodeficiency Syndrome/metabolism , Interleukin-1/biosynthesis , Monocytes/metabolism , Tumor Necrosis Factor-alpha/biosynthesis , Acquired Immunodeficiency Syndrome/enzymology , Cell Line , HIV Antigens/biosynthesis , HIV Core Protein p24 , Humans , Leukemia, Monocytic, Acute/enzymology , Leukemia, Monocytic, Acute/metabolism , Leukemia, Monocytic, Acute/microbiology , Lipopolysaccharides/pharmacology , Monocytes/enzymology , Monocytes/microbiology , RNA-Directed DNA Polymerase/metabolism , Retroviridae Proteins/biosynthesis , Tumor Cells, Cultured/enzymology , Tumor Cells, Cultured/metabolism , Tumor Cells, Cultured/microbiologyABSTRACT
A 58-year-old man, who was entering remission from acute monocytic leukaemia, died unexpectedly after five days of fever. Cultures of necropsy material grew the yeast Trichosporon beigelii, and subsequent histological examination showed a widely disseminated infection. This fungus usually causes a localised lesion of the hair shaft (piedra). Deep-seated infections due to Trichosporon spp. have been recorded infrequently and disseminated infections on only five previous occasions. None of these has been from the United Kingdom. This case report describes some of the difficulties of diagnosis.
Subject(s)
Leukemia, Monocytic, Acute/complications , Mitosporic Fungi , Mycoses/complications , Humans , Leukemia, Monocytic, Acute/microbiology , Leukemia, Monocytic, Acute/pathology , Lung/microbiology , Male , Middle Aged , Mitosporic Fungi/isolation & purification , Mycoses/microbiology , Mycoses/pathology , Spleen/pathologySubject(s)
Leukemia, Monocytic, Acute/ultrastructure , Leukemia, Myeloid, Acute/ultrastructure , Virion/ultrastructure , Bromodeoxyuridine/pharmacology , Cell Line , Culture Media , Cytoplasm/ultrastructure , Dimethyl Sulfoxide/pharmacology , Humans , Leukemia, Monocytic, Acute/microbiology , Leukemia, Myeloid, Acute/microbiologySubject(s)
Leukemia, Lymphoid/complications , Leukemia, Monocytic, Acute/complications , Leukemia, Myeloid, Acute/complications , Sepsis/epidemiology , Autopsy , Humans , Leukemia, Lymphoid/microbiology , Leukemia, Monocytic, Acute/microbiology , Leukemia, Myeloid, Acute/microbiology , Sepsis/microbiologyABSTRACT
Antigens related to the major structural protein (p30) of type C viruses isolated from a woolly monkey and a gibbon ape were found in peripheral white blood cells from five patients with acute leukemia.