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Resident alveolar macrophages are susceptible to and permissive of Coxiella burnetii infection.

Calverley M, Erickson S, Read AJ, Harmsen AG - PLoS ONE (2012)

Bottom Line: Coxiella burnetii, the causative agent of Q fever, is a zoonotic disease with potentially life-threatening complications in humans.We have found that lower doses of both phase I and phase II Nine Mile C. burnetii multiply and are less readily cleared from the lungs of mice compared to higher infectious doses.The low rate of phase I and II Nine Mile C. burnetii growth in murine lungs may be a direct result of the limited size of the susceptible resident AM cell population.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology and Infectious Diseases, Montana State University, Bozeman, MT, USA.

ABSTRACT
Coxiella burnetii, the causative agent of Q fever, is a zoonotic disease with potentially life-threatening complications in humans. Inhalation of low doses of Coxiella bacteria can result in infection of the host alveolar macrophage (AM). However, it is not known whether a subset of AMs within the heterogeneous population of macrophages in the infected lung is particularly susceptible to infection. We have found that lower doses of both phase I and phase II Nine Mile C. burnetii multiply and are less readily cleared from the lungs of mice compared to higher infectious doses. We have additionally identified AM resident within the lung prior to and shortly following infection, opposed to newly recruited monocytes entering the lung during infection, as being most susceptible to infection. These resident cells remain infected up to twelve days after the onset of infection, serving as a permissive niche for the maintenance of bacterial infection. A subset of infected resident AMs undergo a distinguishing phenotypic change during the progression of infection exhibiting an increase in surface integrin CD11b expression and continued expression of the surface integrin CD11c. The low rate of phase I and II Nine Mile C. burnetii growth in murine lungs may be a direct result of the limited size of the susceptible resident AM cell population.

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NMI infected cells expressed CD11c+ and were consistent with a resident AM phenotype.Groups of 5–6 C57BL/6 mice were infected with 1×104 NMI. Twelve days PI, BALF fluid was obtained and histology of cytospin preparations was performed. A) Twelve days PI with 1×104 NMI, infected cells were identified by the presence of Coxiella (stained red) and CD11c expression (stained green). Results were consistent with infected cells being a resident AM phenotype. B) Twelve days PI with 1×104 NMI, BALF cells were adhered to slides and were not stained as a control for autofluorescence. Representative photomicrographs are shown.
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pone-0051941-g008: NMI infected cells expressed CD11c+ and were consistent with a resident AM phenotype.Groups of 5–6 C57BL/6 mice were infected with 1×104 NMI. Twelve days PI, BALF fluid was obtained and histology of cytospin preparations was performed. A) Twelve days PI with 1×104 NMI, infected cells were identified by the presence of Coxiella (stained red) and CD11c expression (stained green). Results were consistent with infected cells being a resident AM phenotype. B) Twelve days PI with 1×104 NMI, BALF cells were adhered to slides and were not stained as a control for autofluorescence. Representative photomicrographs are shown.

Mentions: Given the similarities in the characteristic changes in phenotypic expression of AM subsets throughout the course of NMII and NMI infection, we hypothesized that during NMI infection the resident AM would be the cellular subset susceptible to infection. To test this, we infected groups of 5–6 C57BL/6 mice with 1×104 NMI (dose chosen to match the previous experiment) for 12 days. At 12 days PI, cytospin slides of BALF cells from the two groups of mice were prepared and AM were stained for both C. burnetii and CD11c expression (Figure 8A-representative sample, Figure 8B-negative control).


Resident alveolar macrophages are susceptible to and permissive of Coxiella burnetii infection.

Calverley M, Erickson S, Read AJ, Harmsen AG - PLoS ONE (2012)

NMI infected cells expressed CD11c+ and were consistent with a resident AM phenotype.Groups of 5–6 C57BL/6 mice were infected with 1×104 NMI. Twelve days PI, BALF fluid was obtained and histology of cytospin preparations was performed. A) Twelve days PI with 1×104 NMI, infected cells were identified by the presence of Coxiella (stained red) and CD11c expression (stained green). Results were consistent with infected cells being a resident AM phenotype. B) Twelve days PI with 1×104 NMI, BALF cells were adhered to slides and were not stained as a control for autofluorescence. Representative photomicrographs are shown.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3526480&req=5

pone-0051941-g008: NMI infected cells expressed CD11c+ and were consistent with a resident AM phenotype.Groups of 5–6 C57BL/6 mice were infected with 1×104 NMI. Twelve days PI, BALF fluid was obtained and histology of cytospin preparations was performed. A) Twelve days PI with 1×104 NMI, infected cells were identified by the presence of Coxiella (stained red) and CD11c expression (stained green). Results were consistent with infected cells being a resident AM phenotype. B) Twelve days PI with 1×104 NMI, BALF cells were adhered to slides and were not stained as a control for autofluorescence. Representative photomicrographs are shown.
Mentions: Given the similarities in the characteristic changes in phenotypic expression of AM subsets throughout the course of NMII and NMI infection, we hypothesized that during NMI infection the resident AM would be the cellular subset susceptible to infection. To test this, we infected groups of 5–6 C57BL/6 mice with 1×104 NMI (dose chosen to match the previous experiment) for 12 days. At 12 days PI, cytospin slides of BALF cells from the two groups of mice were prepared and AM were stained for both C. burnetii and CD11c expression (Figure 8A-representative sample, Figure 8B-negative control).

Bottom Line: Coxiella burnetii, the causative agent of Q fever, is a zoonotic disease with potentially life-threatening complications in humans.We have found that lower doses of both phase I and phase II Nine Mile C. burnetii multiply and are less readily cleared from the lungs of mice compared to higher infectious doses.The low rate of phase I and II Nine Mile C. burnetii growth in murine lungs may be a direct result of the limited size of the susceptible resident AM cell population.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology and Infectious Diseases, Montana State University, Bozeman, MT, USA.

ABSTRACT
Coxiella burnetii, the causative agent of Q fever, is a zoonotic disease with potentially life-threatening complications in humans. Inhalation of low doses of Coxiella bacteria can result in infection of the host alveolar macrophage (AM). However, it is not known whether a subset of AMs within the heterogeneous population of macrophages in the infected lung is particularly susceptible to infection. We have found that lower doses of both phase I and phase II Nine Mile C. burnetii multiply and are less readily cleared from the lungs of mice compared to higher infectious doses. We have additionally identified AM resident within the lung prior to and shortly following infection, opposed to newly recruited monocytes entering the lung during infection, as being most susceptible to infection. These resident cells remain infected up to twelve days after the onset of infection, serving as a permissive niche for the maintenance of bacterial infection. A subset of infected resident AMs undergo a distinguishing phenotypic change during the progression of infection exhibiting an increase in surface integrin CD11b expression and continued expression of the surface integrin CD11c. The low rate of phase I and II Nine Mile C. burnetii growth in murine lungs may be a direct result of the limited size of the susceptible resident AM cell population.

Show MeSH
Related in: MedlinePlus