Affiliation:
1. Department of Bacterial Diseases, Walter Reed Army Institute of Research, Washington, D.C. 20307-5100,1 and
2. American Registry of Pathology2 and
3. Department of Infectious and Parasitic Diseases,3 Armed Forces Institute of Pathology, Washington, D.C. 20306-6000
Abstract
ABSTRACT
Entry of opsonized pathogens into phagocytes may benefit or, paradoxically, harm the host. Opsonization may trigger antimicrobial mechanisms such as reactive oxygen or nitric oxide (NO) production but may also provide a safe haven for intracellular replication. Brucellae are natural intramacrophage pathogens of rodents, ruminants, dogs, marine mammals, and humans. We evaluated the role of opsonins in
Brucella
-macrophage interactions by challenging cultured murine peritoneal macrophages with
Brucella melitensis
16M treated with complement- and/or antibody-rich serum. Mouse serum rich in antibody against
Brucella
lipopolysaccharide (LPS) (aLPS) and human complement-rich serum (HCS) each enhanced the macrophage uptake of brucellae. Combinations of suboptimal levels of aLPS (0.01%) and HCS (2%) synergistically enhanced uptake. The intracellular fate of ingested bacteria was evaluated with an optimal concentration of gentamicin (2 μg/ml) to control extracellular growth but not kill intracellular bacteria. Bacteria opsonized with aLPS and/or HCS grew equally well inside macrophages in the absence of gamma interferon (IFN-γ). Macrophage activation with IFN-γ inhibited replication of both opsonized and nonopsonized brucellae but was less effective in inhibiting replication of nonopsonized bacteria. IFN-γ treatment of macrophages with opsonized or nonopsonized bacteria enhanced NO production, which was blocked by
N
G
-monomethyl
l
-arginine (MMLA), an NO synthesis inhibitor. MMLA also partially blocked IFN-γ-mediated bacterial growth inhibition. These studies suggest that primary murine macrophages have limited ability to control infection with
B. melitensis
, even when activated by IFN-γ in the presence of highly opsonic concentrations of antibody and complement. Additional cellular immune responses, e.g., those mediated by cytotoxic T cells, may play more important roles in the control of murine brucellosis.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
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