Monocytes and macrophages require NADPH oxidase activity for killing of the bacterial pathogen Granulibacter bethesdensis

Thursday, October 11, 2012 — Poster Session III
10:00 a.m. – Noon	Natcher Conference Center, Building 45	NIAID	HOST DEF-1

Authors

• J. Chu
• H.H. Song
• K.A. Zarember
• J.I. Gallin

Abstract

Granulibacter bethesdensis, a member of the Acetobacteraceae family, causes recurrent infections in patients with Chronic Granulomatous Disease (CGD), a deficiency in the NADPH oxidase. Clinical treatment of this organism has posed a challenge and persistence in the host has been suspected in some cases. Previous work in our laboratory demonstrated that G. bethesdensis is serum-resistant and incapable of being killed by CGD polymorphonuclear leukocytes (PMN), suggesting a resistance of this organism to non-oxidative killing mechanisms. Given that G. bethesdensis survives in short-lived PMN, we hypothesized that long-term intracellular bacterial survival in the host might rely on longer-lived macrophages and their precursor monocytes. Here we show that normal monocytes and macrophages internalize G. bethesdensis in a serum-dependent manner. Both cell types utilize an NADPH oxidase-dependent bactericidal mechanism against this organism. In monocytes and macrophages from patients with CGD, G. bethesdensis persists and proliferates. Treatment of these cells with interferon-gamma significantly enhances their killing capacity. Interestingly, the antimicrobial activity of monocytes from some CGD patients with specific mutations is also enhanced, suggesting that interferon-gamma might, in some cases, be beneficial for the treatment of infections in vivo.

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