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

Legionella pneumophila (Lp) grow in cultures in human, guinea pig, and mouse macrophages from A/J strain mice. Because exudate macrophages from this strain of mice have been reported deficient in responsiveness to lymphokines, we thought it of interest to document the extent of responsiveness to interferon-gamma in the context of growth restriction of Lp. Peritoneal exudate macrophages were obtained from A/J mice and cultured in either the presence or absence of recombinant interferon-gamma. These cultures were then infected with Lp and the extent of bacterial growth estimated 48 hr later by means of a colony-forming unit (CFU) assay and electron microscopy. Interferon-gamma treatment significantly restricted the number of CFUs in the culture at concentrations as low as 20 U/ml, but did not affect the uptake of bacteria by macrophages. Furthermore, treatment with interferon induced morphological changes consistent with activated macrophages. The involvement of oxygen-dependent mechanisms in phagocyte killing and growth restriction was examined by the use of inhibitors such as superoxide dismutase (SOD) and catalase. Neither one of these inhibitors of toxic oxygen metabolites affected the interferon-gamma-induced suppression of Lp growth. These results suggest that although thioglycolate-induced exudate macrophages from A/J mice support the growth of Lp, these cells readily respond to the activating influence of interferon-gamma. Furthermore, lymphokine treatment does not inhibit Lp uptake by macrophages and apparently restricts the growth of bacteria by mechanisms independent of the activity of toxic oxygen metabolites.
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PMID:Interferon-gamma induced resistance to Legionella pneumophila in susceptible A/J mouse macrophages. 189 14

Legionella pneumophila, the agent of Legionnaires' disease, is a gram-negative facultative intracellular bacterial pathogen that multiplies in human blood monocytes and alveolar macrophages. Interferon-gamma (IFN-gamma)-activated human monocytes inhibit the intracellular multiplication of L. pneumophila but fail to kill the organism. Similarly, erythromycin and rifampin, the drugs of choice in the treatment of Legionnaires' disease, inhibit the growth of L. pneumophila within monocytes without exerting a cidal effect. In this study, we examined the combined effects of IFN-gamma and antibiotics (erythromycin, rifampin, and clindamycin) to determine whether these independently acting agents would synergistically mediate the killing of intracellular L. pneumophila. Each agent alone or in combination was effective in inhibiting the intracellular multiplication of L. pneumophila. However, IFN-gamma and antibiotics together were unable to kill intracellular L. pneumophila, regardless of the sequence in which they were administered to monocytes. Like erythromycin and rifampin, clindamycin, which is highly concentrated in human alveolar macrophages, was capable of inhibiting the intracellular multiplication of L. pneumophila but failed to kill the bacteria in nonactivated or IFN-gamma-activated monocytes. These results demonstrate that intracellular L. pneumophila are highly resistant to the bactericidal effects of both activated monocytes and antibiotics, alone or in combination.
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PMID:Interferon-gamma and antibiotics fail to act synergistically to kill Legionella pneumophila in human monocytes. 313 75

We investigated the difference in natural resistance to Legionella pneumophila infection between aged (18-20-month-old) and young (3-month-old) mice of ddY strain. Aged mice were more susceptible to the bacterial infection than young mice; 50% lethal doses of L. pneumophila for aged and young mice were 2.2 x 10(7) and 8.5 x 10(7) colony forming units (CFU), respectively, after intraperitoneal injection of the bacteria. The bacterial burden in the livers was larger in aged than young mice after a challenge with a sublethal dose of L. pneumophila. However, peritoneal macrophages of aged mice paradoxically had a greater capacity to kill intracellular L. pneumophila than those of young mice. Interferon-gamma (IFN-gamma) production from naive spleen cells was compared after an in vitro stimulation with formalin-killed L. pneumophila. Spleen cells of aged mice produced significantly less IFN-gamma than those of young mice. When anti-murine IFN-gamma monoclonal antibody was administered before the bacterial infection, the subsequent bacterial burden in the livers significantly increased in young but not in aged mice. These data suggest that, in aged mice, IFN-gamma production is depressed at an early phase of L. pneumophila infection and it renders aged mice more susceptible to the infection.
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PMID:Decreased capacity of aged mice to produce interferon-gamma in Legionella pneumophila infection. 856 84