Characterization of the receptor-ligand pathways important for entry and survival of Francisella tularensis in human macrophages

Ashwin Balagopal, Amanda Shearer MacFarlane, Nrusingh Mohapatra, Shilpa Soni, John S. Gunn, Larry S. Schlesinger

Research output: Contribution to journalArticle

Abstract

Inhalational pneumonic tularemia, caused by Francisella tularensis, is lethal in humans. F. tularensis is phagocytosed by macrophages followed by escape from phagosomes into the cytoplasm. Little is known of the phagocytic mechanisms for Francisella, particularly as they relate to the lung and alveolar macrophages. Here we examined receptors on primary human monocytes and macrophages which mediate the phagocytosis and intracellular survival of F. novicida. F. novicida association with monocyte-derived macrophages (MDM) was greater than with monocytes. Bacteria were readily ingested, as shown by electron microscopy. Bacterial association was significantly increased in fresh serum and only partially decreased in heat-inactivated serum. A role for both complement receptor 3 (CR3) and Fcγ receptors in uptake was supported by studies using a CR3-expressing cell line and by down-modulation of Fcγ receptors on MDM, respectively. Consistent with Fcγ receptor involvement, antibody in nonimmune human serum was detected on the surface of Francisella. In the absence of serum opsonins, competitive inhibition of mannose receptor (MR) activity on MDM with mannan decreased the association of F. novicida and opsonization of F. novicida with lung collectin surfactant protein A (SP-A) increased bacterial association and intracellular survival. This study demonstrates that human macrophages phagocytose more Francisella than monocytes with contributions from CR3, Fcγ receptors, the MR, and SP-A present in lung alveoli.

Original languageEnglish (US)
Pages (from-to)5114-5125
Number of pages12
JournalInfection and Immunity
Volume74
Issue number9
DOIs
StatePublished - Sep 2006
Externally publishedYes

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Francisella tularensis
Francisella
Fc Receptors
Macrophages
Macrophage-1 Antigen
Ligands
Survival
Phagocytosis
Pulmonary Surfactant-Associated Protein A
Monocytes
Serum
Lung
Pulmonary Surfactant-Associated Proteins
Collectins
Opsonin Proteins
Tularemia
Mannans
Phagosomes
Alveolar Macrophages
Electron Microscopy

ASJC Scopus subject areas

  • Immunology

Cite this

Characterization of the receptor-ligand pathways important for entry and survival of Francisella tularensis in human macrophages. / Balagopal, Ashwin; MacFarlane, Amanda Shearer; Mohapatra, Nrusingh; Soni, Shilpa; Gunn, John S.; Schlesinger, Larry S.

In: Infection and Immunity, Vol. 74, No. 9, 09.2006, p. 5114-5125.

Research output: Contribution to journalArticle

Balagopal, Ashwin ; MacFarlane, Amanda Shearer ; Mohapatra, Nrusingh ; Soni, Shilpa ; Gunn, John S. ; Schlesinger, Larry S. / Characterization of the receptor-ligand pathways important for entry and survival of Francisella tularensis in human macrophages. In: Infection and Immunity. 2006 ; Vol. 74, No. 9. pp. 5114-5125.
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