The Compromised Host and Legionnaires' Disease

Saravolatz, Louis D.; Burch, Keith H.; Fisher, Evelyn; Madhavan, T.; Kiani, Daria; Neblett, Thomas R.; Quinn, Edward

doi:10.7326/0003-4819-90-4-533

Cited by 100 publications

(23 citation statements)

References 6 publications

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“…We have found that egg yolk-grown L. pneumophila are resistant to killing by complement even in the presence of anti-L. pneumophila antibody and are inefficiently killed by human polymorphonuclear leukocytes in the presence of anti-L. pneumophila antibody and serum. These results, viewed in conjunction with the increased incidence of L. pneumophila infections in immunosuppressed patients (14)(15)(16), suggest that cell-mediated immunity may play an important role in host defense against L. pneumophila as it does against other intracellular parasites.…”

Section: Resultsmentioning

confidence: 65%

“…It affects all age groups, but particularly people over 30 yr, and men more often than women (8,13). It has a predilection for people who smoke or abuse alcohol, travellers, construction workers, and immunocompromised patients (6,10,(14)(15)(16), and it is probably spread by the airborne route (10). The case-fatality rate has been in the 15-20% range (10,17).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Legionnaires' Disease Bacterium (Legionella pneumophila) Multiplies Intracellularly in Human Monocytes

Horwitz¹,

Silverstein²

1980

J. Clin. Invest.

629

524

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A B S T R A C T We have studied the interaction between virulent egg yolk-grown Legionella pneumophila Philadelphia 1 and human blood monocytes in vitro. The leukocytes were cultured in antibiotic-free tissue culture medium supplemented with 15% autologous human serum.L. pneumophila multiplied several logs, as measured by colony-forming units, when incubated with monocytes or mononuclear cells; the mid-log phase doubling time was 2 h. The level to which L. pneumophila multiplied was proportional to the number of mononuclear cells in the culture. L. pneumophila multiplied only in the adherent fraction of the mononuclear cell population indicating that monocytes but not lymphocytes support growth of the bacteria. Peak growth ofL. pneumophila was correlated with destruction of the monocyte monolayer. By fluorescence microscopy using fluorescein conjugated rabbit anti-L. pneumophila antiserum, the number of monocytes containing L. pneumophila increased in parallel with bacterial growth in the culture. At the peak of infection, monocytes were packed full with organisms. By electron microscopy, L. pneumophila in such monocytes were found in membrane-bound cytoplasmic vacuoles studded with structures resembling host cell ribosomes.

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Section: Resultsmentioning

confidence: 65%

Section: Introductionmentioning

confidence: 99%

Legionnaires' Disease Bacterium (Legionella pneumophila) Multiplies Intracellularly in Human Monocytes

Horwitz¹,

Silverstein²

1980

J. Clin. Invest.

629

524

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“…Legionnaires' disease has a predilection for immunocompromised patients (36)(37)(38)(39). Our findings suggest that a defect in cell-mediated immunity may be responsible for this by rendering such patients less capable of limiting the multiplication of Legionnaires' disease bacteria to which they are exposed.…”

Section: Cell-mediated Immunity May Be Viewed As Having An Afferent Amentioning

confidence: 78%

Activated human monocytes inhibit the intracellular multiplication of legionnaires' disease bacteria

Horwitz¹,

Silverstein²

1981

The Journal of Experimental Medicine

137

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We have examined the interaction between virulent egg yolk-grown L. pneumophila, Philadelphia 1 strain, and in vitro-activated human monocytes, under antibiotic-free conditions. Freshly explanted human monocytes activated by incubation with concanavalin A (Con A) and human lymphocytes inhibited the intracellular multiplication of L. pneumophila. Both Con A and lymphocytes were required for activation. Con A was consistently maximally effective at greater than or equal to 4 μg/ml. Monocytes activated by incubation with cell-free filtered supernatant from Con A-sensitized mononuclear cell cultures also inhibited the intracellular multiplication of L. pneumophil a. The most potent supernatant was obtained from mononuclear cell cultures incubated with greater than or equal to 15 μg/ml Con A for 48 h. The degree of monocyte inhibition of L. pneumophila multiplication was proportional to the length of time monocytes were preincubated with supernatant (48 {greater than} 24 {greater than} 12 h) and to the concentration of supernatant added (40 percent {greater than} 20 percent {greater than} 10 percent {greater than} 5 percent). Monocytes treated with supernatant daily were more inhibitory than monocytes treated initially only. With time in culture, monocytes progressively lost a limited degree of spontaneous inhibitory capacity and also lost their capacity to respond to supernatant with inhibition of L. pneumophila multiplication. Supernatant-activated monocytes inhibited L. pneumophila multiplication in two ways. They phagocytosed fewer bacteria, and they slowed the rate of intracellular multiplication of bacteria that were internalized. As was the case with nonactivated monocytes, antibody had no effect on the rate of intracellular multiplication in supernatant-activated monocytes. Neither supernatant-activated nor nonactivated monocytes killed L. pneumophila in the absence of antibody. Both killed a limited proportion of these bacteria in the presence of antibody and complement. We have previously reported that anti-L, pneumophila antibody and complement neither promote effective killing of L. pneumophila by human polymorphonuclear leukocytes and monocytes nor inhibit the rate of L. pneumophila multiplication in monocytes. These findings and our present report that activated monocytes do inhibit L. pneumophila multiplication indicate that cell-mediated immunity plays a major role in host defense against Legionnaires' disease.

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“…Legionnaires' disease in the immunocompromised host is often acquired from a nosocomial source. Fever, malaise, and a productive cough are common 8 . Radiographically, the presence of bilateral infiltrates and cavitation is relatively frequent.…”

Section: Pulmonary Infections In Cancer Patientsmentioning

confidence: 99%