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Query: UMLS:C0023241 (Legionella)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum samples from 14 patients with Legionella pneumonia were examined for the presence of cytokines. In spite of high levels of serum C-reactive protein in all patients during the acute phase in only four cases (one involving interleukin-1beta [IL-1beta], three involving IL-6, and none involving tumor necrosis factor alpha) was the concentration of cytokines more than 100 pg/ml. Th2 cytokines IL-4 and IL-10 were detected in only one patient each. In contrast, significant increases of serum gamma interferon (IFN-gamma) and IL-12 levels were observed during the acute phase in 6 and 11 cases, respectively. Interestingly, although serum IFN-gamma levels diminished thereafter, in seven cases IL-12 levels remained high or increased further during the convalescent phase. In an additional 22 cases clinically suspected to be but not diagnosed as Legionella pneumonia, increases of serum IL-12 levels were observed in 16 cases, whereas the remaining 6 cases showed no detectable IL-12. Our results demonstrate the relative predominance of Th1 cytokine production in Legionella pneumonia. Although the role and significance of prolonged increases in IL-12 levels in Legionella disease are unknown, our results should prompt further investigation of the host immune response in terms of Th1 and Th2 balance in legionellosis.
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PMID:Serum cytokines in patients with Legionella pneumonia: relative predominance of Th1-type cytokines. 960 98

The influence of marijuana cannabinoids on immune function has been examined extensively over the last 25 yr. Various experimental models have been used employing drug-abusing human subjects, experimental animals exposed to marijuana smoke or injected with cannabinoids, and in vitro models employing immune cell cultures treated with various cannabinoids. For the most part, these studies suggest that cannabinoids modulate the function of T and B lymphocytes as well as NK cells and macrophages. In addition to studies examining cannabinoid effects on immune cell function, other reports have documented that these substances modulate host resistance to various infectious agents. Viruses such as herpes simplex virus and murine retrovirus have been studied as well as bacterial agents such as members of the genera Staphylococcus, Listeria, Treponema, and Legionella. These studies suggest that cannabinoids modulate host resistance, especially the secondary immune response. Finally, a third major area of host immunity and cannabinoids is that involving drug effects on the cytokine network. Employing in vivo and in vitro models, it has been determined that cannabinoids modulate the production and function of acute phase and immune cytokines as well as modulate the activity of network cells such as macrophages and T helper cells, Th1 and Th2. These results are intriguing and demonstrate that under certain conditions, cannabinoids can be immunomodulatory and enhance the disease process. However, more studies are needed to determine both the health risk of marijuana abuse and the role of the cannabinoid receptor/ligand system in immune regulation and homeostasis.
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PMID:Marijuana, immunity and infection. 961 Jun 78

Legionella pneumophila, the causative agent of legionnaires' disease, is a gram-negative pleomorphic bacillus and fastidious in its growth in artificial medium. These bacteria grow readily intracellularly, including growth in macrophages and other phagocytic cells. Humoral antibodies develop readily to these bacteria not only in infected patients, but also in persons who have had subclinical exposure. High-levels of serum antibodies may also occur in individuals who recover from infection. However, cell-mediated immunity based on lymphocytes reacting with the organisms and cytokines produced by such lymphocytes are important in resistance. Vaccines prepared from killed Legionella or their components readily induce cell-mediated immunity. Immune resistance to disease depends on lymphocyte-based immunity, activating cytokine formation, some of which activate macrophages to resist infection. Resistance to Legionella infection by experimental animals such as mice correlates with activation of macrophages, which can inhibit replication of the bacteria. Much recent experimental work has involved studies using inbred animals, including inbred mice genetically resistant to Legionella versus mice genetically susceptible. Detailed studies show that regulation of macrophage resistance versus susceptibility to infection is mediated by specific genetic mechanisms. Induction of cytokines by Legionella can activate immune cells, especially helper T cells. Th 1 type helper cells that produce type 1 class cytokines, such as interferon gamma and interleukin-2 (IL-2), are known to be important in cellular immunity to Legionella as well as to other opportunistic intracellular bacteria. In contrast, Th 2 type helper cells, which secrete type 2 class cytokines such as IL-4, IL-5, and IL-6, activate B lymphocytes to produce humoral antibodies important in resistance to extracellular bacteria which secrete toxins and extracellular factors as compared to intracellular bacteria such as Legionella. Although Legionella, similar to other ubiquitous opportunistic pathogens, can cause serious infection in immunocompromised individuals, these bacteria have many distinguishing characteristics, such as very rapid replication in macrophages from susceptible individuals. However, activated macrophages restrict the growth of these bacteria. Infection by Legionella, if recognized clinically, can be readily treated with appropriate antibiotics. Currently, many studies are in progress concerning the mechanism of pathogenicity and assessment of the molecular biologic mechanisms of protective immune responses to this bacterium, which causes serious infection in immunocompromised individuals.
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PMID:Immunologic response and pathophysiology of Legionella infection. 964 87

Legionella pneumophila, a gram-negative bacterium causing Legionnaires' disease and Pontiac fever, was shown to be highly reactive in in vitro gelation of Limulus lysate but not able to induce fever and the local Shwartzman reaction in rabbits and mice. We analyzed the capacity of purified L. pneumophila lipopolysaccharide (LPS-Lp) to induce activation of the human monocytic cell line Mono Mac 6, as revealed by secretion of proinflammatory cytokines and desensitization to subsequent LPS stimulation. We showed that despite normal reactivity of LPS-Lp in the Limulus amoebocyte lysate assay, induction of cytokine secretion in Mono Mac 6 cells and desensitization to an endotoxin challenge required LPS-Lp concentrations 1,000 times higher than for LPS of Salmonella enterica serovar Minnesota. Therefore, we examined the interaction of LPS-Lp with the LPS receptor CD14. We demonstrated that LPS-Lp did not bind to membrane-bound CD14 expressed on transfected CHO cells, nor did it react with soluble CD14. Our results suggest that the low endotoxic potential of LPS-Lp is due to a failure of interaction with the LPS receptor CD14.
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PMID:Low endotoxic potential of Legionella pneumophila lipopolysaccharide due to failure of interaction with the monocyte lipopolysaccharide receptor CD14. 971 61

The marijuana cannabinoid, delta 9-tetrahydrocannabinol (THC), suppresses immunity to Legionella pneumophila and development of Th1 activity and cell-mediated immunity. In the current study, THC effects on cytokines regulating the development of Th1 cells were examined. BALB/c mice showed significant increases in serum IL-12 and IFN-gamma within hours of infection; however, the levels of these Th1-promoting cytokines as well as resistance to a challenge infection were suppressed by THC (8 mg/kg) injected 18 h before priming. The Th2-promoting cytokine, IL-4, was increased within hours of a Legionella infection and was further increased by THC treatment. These results suggested that THC injection suppressed the cytokine environment promoting Th1 immunity. In additional experiments, THC pretreatment and infection of IL-4 knockout mice showed that serum IL-12 and IFN-gamma were suppressed equally in both knockout and normal mice. This suggested that the drug-induced increase in IL-4 was not responsible for the decreases in serum IL-12 and IFN-gamma. However, THC treatment was shown to suppress the expression of IL-12 receptor beta 2 mRNA, indicating that, in addition to suppression of IL-12, THC injection suppressed the expression of IL-12 receptors. Finally, the role of cannabinoid receptors in Th1-promoting cytokine suppression was examined, and results with receptor antagonists showed that both cannabinoid receptors 1 and 2 were involved. It is suggested that suppression of Th1 immunity to Legionella is not due to an increase in IL-4 production but to a decrease in IFN-gamma and IL-12. Furthermore, both types of cannabinoid receptors are involved.
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PMID:Delta 9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma, IL-12, and IL-12 receptor beta 2 responses to Legionella pneumophila infection. 1084 2

Virulent Legionella pneumophila replicate readily in thioglycollate-elicited peritoneal macrophages from genetically permissive A/J mice, but avirulent L. pneumophila do not. The production of cytokines by macrophages infected with L. pneumophila has been studied, but the correlation of bacterial virulence with immune responses of macrophages, such as proinflammatory cytokine production, is not well understood. In this regard, production of the cytokines tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1alpha, IL-1beta, and IL-6 were examined in macrophage cultures infected in vitro with virulent vs. avirulent L. pneumophila. Infection of macrophages from A/J mice with the virulent L. pneumophila up-regulated mRNA expression for these cytokines, whereas avirulent bacteria resulted in only a slight or no detectable increase in cytokine mRNA. Similarly, virulent L. pneumophila induced the macrophages to produce relatively high levels of TNF-alpha, IL-1alpha, IL-1beta, and IL-6 proteins as measured by enzyme-linked immunosorbent assays, whereas avirulent bacteria induced only low or often undetectable amounts of these cytokines. Thus, these results show the murine macrophages from susceptible A/J mice are readily infected with virulent L. pneumophila in vitro and stimulated to produce the proinflammatory acute-phase cytokines TNF-alpha, IL-1alpha, IL-1beta, and IL-6, but avirulent L. pneumophila did not. Such differences in induction of these proinflammatory cytokines by macrophages in response to virulent vs. avirulent L. pneumophila infections may be an important factor in the pathogenesis induced by these intracellular bacteria.
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PMID:Murine macrophages differentially produce proinflammatory cytokines after infection with virulent vs. avirulent Legionella pneumophila. 1085 60

Legionella pneumophila is an ubiquitous opportunistic intracellular pathogen that replicates readily in thioglycollate-elicited peritoneal macrophages from genetically susceptible A/J mice. Treatment of macrophage cultures in vitro with tumor necrosis factor-alpha (TNF-alpha) induced resistance of the macrophages to infection by Legionella as compared with control macrophages treated with medium alone. Addition of small amounts of monoclonal antibody to TNF-alpha restored susceptibility of the macrophages. Furthermore, antibody to the proinflammatory cytokine interleukin-1 (IL-1) alpha/beta increased resistance, but recombinant IL-1 had little effect. Such decreased susceptibility to Legionella growth in anti-IL-1 antibody-treated cultures corresponded with enhanced levels of TNF-alpha in the supernatants of the treated cells. An antibody to another proinflammatory cytokine with known immunoregulatory properties (i.e., IL-6) had little or no effect on the ability of the macrophages to be infected by Legionella and, furthermore, treatment with recombinant IL-6, similar to recombinant IL-1, did not modify the ability of the cells to be infected in vitro. These results indicate that TNF-alpha is important in controlling L. pneumophila replication, and IL-1 can regulate TNF-alpha levels, affecting susceptibility of macrophages to infection with an intracellular opportunistic pathogen like Legionella.
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PMID:Tumor necrosis factor induces resistance of macrophages to Legionella pneumophila infection. 1086 36

Mycobacterium tuberculosis is one of the intracellular parasitic bacteria escaping the intracellular killing inside macrophages. The aim of this symposium was to get some insight into the mechanism of pathogenicity and host defense in M. tuberculosis infection, which has not yet been elucidated well, by the presentation of up-to-date knowledge on these aspect in infection with different intracellular parasitic microbes. Dr. Yoshikai (Nagoya Univ.) indicated that TLR is involved in the initial response of host against S. choleraesuis. Among the cytokines contributing to the induction of specific immunity, the importance of IL-15 was emphasized, based on their own experimental data using IL-15 transgenic mice and the application of anti-IL-15 antibody in vivo. Dr. Yoshida (Kyushu Univ.) reviewed the mechanisms of intracellular growth of Legionellae. Several genes so far identified as essential genes in intra-macrophage growth appeared to be similar to those encoding type 3 secretion system observed in Shigellae. There is a significant strain difference in the growth of L. pneumophila inside macrophages and such difference seemed to be under the control of a gene at chromosome 13, Lgn 1. The investigation of difference in the mode of escape among various Legionella. spp. may provide a novel mechansim in bacterial invasion and escape. Dr. Kawamura (Kyoto Univ.) summarized some new reports on the molecular mechanism of the inhibition of P-L fusion by M. tuberculosis. He emphasized the importance of the alteration in phagosomal maturation as indicated by the accumulation of TACO protein. The possible involvement of TLR in the recognition of Mycobacterial cells and its LAM was discussed. Dr. Kawakami (Ryukyu Univ.) first discussed the possibility that Cryptococcus neoformans, a fungal pathogen, could be regarded as one of the intracellular parasitic microbes. His presentation mainly focused on the TH1-Th2 balance in the expression of host defense against C. neoformans in mice. From their experimental infection using attenuated strain TC-13 in various cytokine-knock out mice, the pivotal role of both IL-12 and IL-18 was clearly indicated.
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PMID:[Mechanisms of pathogenicity and host defense in infections by intracellular parasitic microbes]. 1106 72

Infection of macrophages from genetically susceptible A/J mice with Legionella pneumophila induces high levels of various cytokines in serum as well as in cultures of spleen or peritoneal cells from the mice. However, modulation of receptor expression for these cytokines during infection has not been studied in detail, even though these receptors on macrophages have a critical role in inflammatory responses during the infection. In the present study, the differential expression of mRNA for TNF and IL-1 receptors as well as receptor antigens during infection of macrophages with virulent vs. avirulent L. pneumophila was investigated. Mouse thioglycollate-elicited peritoneal macrophages showed by RT-PCR constitutive steady-state levels of mRNA for TNF-type I and -type II receptors as well as IL-1 type I receptor. However, IL-1 type II receptor mRNA was not expressed in thioglycollate-elicited macrophages. Infection of macrophages with virulent bacteria caused an upregulation of IL-1 type I and TNF type I receptor mRNA, but had no effect on TNF type II receptor message. Avirulent L. pneumophila infection caused much less induction of these receptor mRNAs. The amount of receptor antigen of IL-1 type I on the surface of macrophages was also increased by infection with virulent L. pneumophila determined by flow cytometric analysis. These results indicate that L. pneumophila infection not only causes induction of various cytokines, but also modulation of certain cytokine receptors, which may regulate the susceptibility to infection.
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PMID:Differential expression of IL-1 and TNF receptors in murine macrophages infected with virulent vs. avirulent Legionella pneumophila. 1106 74

Gamma interferon (IFN-gamma), a pleiotropic cytokine, is now known to be produced by macrophages as well as by NK cells, gammadelta cells, and activated T cells. The autocrine biological functions of IFN-gamma on the macrophage include the upregulation of major histocompatibility complex MHC class II and the activation to an antiviral state. In this study, the production of IFN-gamma by macrophages was demonstrated to correspond to antibacterial activity. Legionella pneumophila replicates intracellularly in thioglycolate (TG)-elicited macrophages (TG-macrophages) from A/J mice, while TG-macrophages from BALB/c mice restrict bacterial growth after an initial period of growth. BALB/c TG-macrophages were shown to express IFN-gamma mRNA at 24 and 28 h, which corresponded to the initiation of anti-L. pneumophila activity. Moreover, IFN-gammaneutralization by antibody treatment of the cultures resulted in increased L. pneumophila growth in the macrophages. In contrast, no IFN-gamma mRNA was expressed in TG-macrophages from A/J mice, where L. pneumophila grew unrestricted. As would be expected, IFN-gamma treatment decreased bacterial growth. An IFN-gamma-mediated antibacterial activity was, however, inducible in A/J macrophages by the addition of interleukin-12 following L. pneumophila infection. Thus, autocrine IFN-gamma is involved in anti-L. pneumophila activity associated with different growth patterns and appears to be important during intracellular infection.
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PMID:Differential induction of gamma interferon in Legionella pneumophila-infected macrophages from BALB/c and A/J mice. 1134 20


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