Contemplating the murine test tube: lessons from natural killer cells and<i>Cryptococcus neoformans</i>

Marr, Kaleb J.; Jones, Gareth; Mody, Christopher H.

doi:10.1111/j.1567-1364.2006.00096.x

Cited by 4 publications

(3 citation statements)

References 146 publications

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“…Nitrite production by these cells, however, totally depended on substitution of the cofactor BH4 and additional substrate [15]. As species differences are not confined to NOS activity and are fundamental in many aspects of immunology [3,16,17], we propose that the species involved should be mentioned in the title and abstract of articles dealing with common aspects of immunity.…”

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confidence: 99%

Macrophage biology and immunology: man is not a mouse

Schneemann

Schoeden

2007

Journal of Leukocyte Biology

145

122

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A recent article by Shibata et al. [1] and an interview with the senior investigator Kobayashi [2], both in the October 2006 issue of Journal of Leukocyte Biology, discuss the role of macrophage-derived NO in the clearance of apoptotic cells. We were surprised that neither in the original paper nor in the accompanying interview was it discussed that these results rely entirely on data obtained in murine macrophages. It is, however, evident that there are differences in macrophage NO production and regulation among different species [3,4]. Several years ago, we and others [5][6][7] described fundamental differences between macrophages from mice and humans regarding NO synthase (NOS) activity. Murine macrophages produce large amounts of NO and L-citrulline from L-arginine via induction of the inducible form of NOS (iNOS). In parallel, murine macrophages synthesize the obligatory cofactor tetrahydrobiopterin (BH4), essential for stabilization and function of the iNOS enzyme protein [8,9]. Human as well as macrophages from other animal species, such as rabbits, goats, or Syrian hamsters, do not have NOS activity nor do they synthesize BH4 [7,10,11]. In addition, murine macrophages consume most of the L-arginine by another enzyme-arginase-and convert it into L-ornithine. This arginase is not active in human macrophages too [7,9,12]. A lot of research has since been done to demonstrate nitrite production in human macrophages. Recent reviews claim that human macrophages have iNOS activity, albeit induced by other stimuli rather than those inducing nitrite production in murine macrophages [13]. We evaluated several of these stimuli and could show that nitrite was not produced by iNOS activity in human macrophages. The nitrite measured came from other noncellular sources [14]. None of the articles cited as proof for iNOS activity in human macrophages provides sound biochemical data about L-arginine consumption, BH4 synthesis, and L-citrulline production [13]. Moreover, they do not control for nitrite generation from other nonmacrophage sources [14]. The only report that demonstrates nitrite production from NOS activity in human macrophage-like cells is an article by Bertholet et al. [15]. There, the U937 monoblastic leukemia cell line was transfected with a plasmid containing a functional iNOS gene. Nitrite production by these cells, however, totally depended on substitution of the cofactor BH4 and additional substrate [15]. As species differences are not confined to NOS activity and are fundamental in many aspects of immunology [3,16,17], we propose that the species involved should be mentioned in the title and abstract of articles dealing with common aspects of immunity.

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confidence: 99%

Macrophage biology and immunology: man is not a mouse

Schneemann

Schoeden

2007

Journal of Leukocyte Biology

145

122

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“…Polymorphonuclear (PMN) cells, also known as neutrophils, are effective phagocytic cells in the early stages of infection and may serve the immune system best by containing a chronic C. neoformans infection (35). In a recent study, Marr K. et al (36) explored the similarities and differences of natural killer (NK) cells anticryptococcal activity between humans and mice. NK cells can play different roles in humans than in mice during cryptococcal infection and vary in respect to their distribution in the body, cytokine interaction, receptor expression and their interaction with a variety of other effecter molecules (36,37).…”

Section: Complement-mediated Andnon-specific Cellular Immunitymentioning

confidence: 99%

“…In a recent study, Marr K. et al (36) explored the similarities and differences of natural killer (NK) cells anticryptococcal activity between humans and mice. NK cells can play different roles in humans than in mice during cryptococcal infection and vary in respect to their distribution in the body, cytokine interaction, receptor expression and their interaction with a variety of other effecter molecules (36,37). However, macrophages undoubtedly play an essential role in C. neoformans phagocytosis throughout the duration of the infection in humans and mice.…”

Section: Complement-mediated Andnon-specific Cellular Immunitymentioning

confidence: 99%

Protective Immunity Against Cryptococcus Neoformans Infection

Schop

2020

MJM

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Cryptococcus neoformans, the etiological agent of cryptococcosis, is an occasional opportunistic fungal pathogen of immune competent individuals. However, it is a relatively frequent cause of life-threatening meningoencephalitis and pulmonary infections in immunosuppressed hosts and is a leading mycological cause of morbidity and mortality among patients with AIDS in most parts of the world. The lack of an effective fungicidal regimen and the development of antifungal resistant strains suggest that continued investigation is necessary to devise immunotherapeutic strategies, drug targets and/or vaccines to combat C. neoformans infections. Until recently, cryptococcal virulence factors such as its polysaccharide capsule, macrophage parasitism, and its ability to induce an ineffective antibody mediated immune (AMI) response along with a non-protective type II (Th2) cell-mediated immune response have thwarted efforts to induce complete protective immunity against a lethal cryptococcal strain in murine models. The presence of C. neoformans antibodies in adult human serum suggests that immune competent individuals have difficulty resolving an early cryptococcal infection allowing for the establishment of a subclinical chronic infection. Recent studies have shown that pro-inflammatory cytokines, specifically interferon-g (IFN-g), associated with type I (Th1) cell-mediated immunity can successfully drive cell-mediated immune (CMI) responses to produce protective immunity to a second experimental C. neoformans infection in mice. This review will evaluate the intricacies of the host-cryptococcal interaction and discuss recent developments in C.neoformans research and the potential for human vaccines and/or drug therapies.

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Current awareness on yeast

2006

Yeast

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In order to keep subscribers up‐to‐date with the latest developments in their field, this current awareness service is provided by John Wiley & Sons and contains newly‐published material on yeasts. Each bibliography is divided into 10 sections. 1 Books, Reviews & Symposia; 2 General; 3 Biochemistry; 4 Biotechnology; 5 Cell Biology; 6 Gene Expression; 7 Genetics; 8 Physiology; 9 Medical Mycology; 10 Recombinant DNA Technology. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted. (4 weeks journals ‐ search completed 9th. Aug. 2006)

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Contemplating the murine test tube: lessons from natural killer cells andCryptococcus neoformans

Cited by 4 publications

References 146 publications

Macrophage biology and immunology: man is not a mouse

Macrophage biology and immunology: man is not a mouse

Protective Immunity Against Cryptococcus Neoformans Infection

Current awareness on yeast

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