Role of Polymorphonuclear Leukocytes in the Resistance of Tumor-Bearing Mice against Candida albicans Infection

Abstract

Opportunistic fungal infection occurring frequently in a compromised host is one of the most important problems in modern medicine, because of the difficulty of treatment and the frequency with which such infections progress to a lifethreatening condition. There are many papers reports on the increased susceptibility of tumor-bearing hosts to systemic fungal infections. [2][3][4][5][6] The protective activity of allogeneic sarcoma 180 tumor-bearing mice against Candida albicans and Aspergillus fumigatus infections has been reported in our previous papers. [7][8][9][10][11] It has also been reported that there is a significant delay in the lethal response to C. albicans in mice bearing Lewis lung carcinoma. 12) However, the mechanisms of such an effect have yet to be fully elucidated. We reported that the number of peripheral blood polymorphonuclear leukocytes (PMNs) dramatically increased in sarcoma 180 tumor-bearing mice. [7][8][9] We also investigated the producibility of the granulocyte-macrophage colony-stimulating factor from the tumor cells. 9,10) We thought that this phenomenon should be investigated not only in allogeneic tumor-bearing mice but also in syngeneic tumor-bearing mice. In the present study, to demonstrate further the importance of PMNs in the resistance of tumor-bearing mice against C. albicans, we conducted a protection assay against the infection using allogeneic (sarcoma 180) and syngeneic (Meth A fibrosarcoma [Meth A] and MM 46 mammary carcinoma [MM46]) solid tumor-bearing mice over the course of 3 weeks after tumor cell transplantation. Furthermore, we investigated in detail the involvement of PMNs from tumor-bearing mice as the likely mechanism of such protection. MATERIALS AND METHODS Mice and TumorsMale 6-to 8-week-old ddY, BALB/c, and C3H/He mice were obtained from the Shizuoka Laboratory Animal Center, Hamamatsu, Japan. Sarcoma 180 (1ϫ10 6 ), 3-methylcholanthrene-induced Meth A fibrosarcoma (Meth A, 1ϫ10 6 ), and MM 46 mammary carcinoma (MM46, 3ϫ10 6 ) were transplanted subcutaneously in the ddY, BALB/c, and C3H/He mice, respectively. Cyclophosphamide (CY)-treated mice were prepared as follows: 16 d after tumor transplantation, the mice were injected intraperitoneally with a single dose of 15, 50, or 200 mg/kg of CY (Cytoxan, Shionogi Co., Ltd., Osaka, Japan).Fungus The C. albicans NIH A-207 strain was kindly donated by Dr. T. Shinoda, Department of Microbiology, Meiji College of Pharmacy, Tokyo, Japan, and was maintained on Sabouraud agar slants. For this study, the fungus was cultured in a Sabouraud liquid medium which was shaken at 27°C for 48 h.Infection-Protection Assay One, 2, and 3 weeks after tumor cell transplantation, the mice were inoculated intravenously with 2ϫ10 6 viable C. albicans cells. The mice bearing only the solid tumor began dying by week 4; therefore reliable data could not be obtained beyond 3 weeks. In the CY experiment, 4 d after CY administration, the mice were infected intravenously with the fungal cells. The mortality rate of the mice was recorded for...

Influence of Tumour Condition on the Macrophage Activity in Candida albicans Infection

“…These data demon-strate that there was an increase in H 2 O 2 release at the beginning of the neoplastic progression, but after this period, H 2 O 2 production decreased and the infection spread. Our findings are consistent with those described by Okawa et al [7], who verified that the C. albicans load in sarcoma-bearing mice was related to the levels of oxygen metabolites released by polymorphonuclear cells.…”

“…Our findings are consistent with those described by Okawa et al. [7], who verified that the C. albicans load in sarcoma‐bearing mice was related to the levels of oxygen metabolites released by polymorphonuclear cells.…”

“…Candida albicans systemic infections have an important impact on the clinical course and outcomes of cancer patients [1, 2], as they are responsible for prolonged hospital stays, high healthcare costs and significant mortality [3–6]. Several authors have disagreed with the widely held belief that compromised immune responses are a cause of the susceptibility to infection in tumour patients, and they have reported that the tumoral condition can generate a protective response against this pathogen [7]. Considering that this phenomenon could be associated with the activation state of macrophages, we decided to study this premise using peritoneal macrophages.…”

Modulation of macrophage cytokine profiles during solid tumor progression: susceptibility to Candida albicansinfection

“…Although a compromised immune response has been invoked as a cause of susceptibility to major infections in tumor-bearing patients, some authors disagree, arguing that the tumoral condition may, inter alia , result in active protection against opportunist pathogens [7]. As most knowledge about Candida infections in cancer patients has been obtained from patients with hematological malignancies [8], and since candidemia is an important complication in patients with solid tumors, we decided to study this premise using peritoneal macrophages in mice bearing solid Ehrlich tumors and infected with C. albicans .…”

“…Numerous studies have described a significant decrease in macrophage functions in tumor-bearing hosts [7]. Since we found no account in the literature about the role of cytokines in the development of solid tumors, and since there are divergent views about the evolution and gravity of C. albicans infection under such circumstances, we proposed to investigate those questions, evaluating the kinetics of cytokine production in mice that bore solid Ehrlich tumors (BTM) and were infected or not infected with the fungus.…”