Resident Alveolar Macrophages Are Susceptible to and Permissive of Coxiella burnetii Infection

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.

Murine Alveolar Macrophages Are Highly Susceptible to Replication of Coxiella burnetii Phase IIIn Vitro

“…In support of our data showing the increased replication of C. burnetii in AMs, it was previously reported that tissue-resident AMs are susceptible to C. burnetii replication in vivo (12). Moreover, human AMs were shown to support C. burnetii replication in culture (11).…”

“…Because most of the gene-deficient mice generated thus far were constructed in the C57BL/6 mouse background, we aimed to identify a primary cell that supported the replication of C. burnetii phase II in culture. It is known that C. burnetii infects macrophages and monocytes, with AMs considered the primary target cell of infection (10,12,(19)(20)(21)(22). Thus, we evaluated whether murine AMs from the C57BL/6 mouse strain support the replication of C. burnetii phase II in culture.…”

“…Interestingly, it was also observed that, within human AMs, C. burnetii more frequently forms multiple smaller CCVs rather than the large fusogenic vacuole observed in other cellular models of infection (11). Within a murine model of infection, it has been demonstrated that AMs are susceptible to C. burnetii infection (12), and an early study demonstrated that nitric oxide (NO) is produced by murine AMs in response to infection (13).…”

Right on Q: Genetics begin to Unravel Coxiella Burnetii host cell Interactions

“…The primary target of Coxiella during natural infection is alveolar macrophages [32,[41][42][43]. The organism can subsequently disseminate to colonize and replicate in resident macrophages of different tissues and organs [44].…”

Differential Macrophage Polarization from Pneumocystis in Immunocompetent and Immunosuppressed Hosts: Potential Adjunctive Therapy during Pneumonia

“…The potential cellular targets for immune modulation to treat PcP include CD4 T cells, CD8 T cells, regulatory T cells, neutrophils, macrophages, and epithelial cells (24,25). Macrophages offer a novel approach to cell therapy in the treatment of infection, especially in the immunosuppressed hosts, but require additional investigation (26)(27)(28)(29)(30)(31). There are relatively few reports concerning macrophage polarization and the resulting antifungal and anti-inflammatory activity as a potential treatment approach for fungal infections (12,32,33).…”