Affiliation:
1. Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130-3932
2. Depatment of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, North Carolina 27834
Abstract
ABSTRACT
Cells in the
Brucella
spp. are intracellular pathogens that survive and replicate within host monocytes.
Brucella
maintains persistent infections in animals despite the production of high levels of anti-
Brucella
-specific antibodies. To determine the effect of antibody opsonization on the ability of
Brucella
to establish itself within monocytes, the intracellular trafficking of virulent
Brucella abortus
2308 and attenuated
hfq
and
bacA
mutants was followed in the human monocytic cell line THP-1. Early trafficking events of
B. abortus
2308-containing phagosomes (BCP) were indistinguishable from those seen for control particles (heat-killed
B. abortus
2308, live
Escherichia coli
HB101, or latex beads). All phagosomes transiently communicated the early-endosomal compartment and rapidly matured into LAMP-1
+
, cathepsin D
+
, and acidic phagosomes. By 2 h postinfection, however, the number of cathepsin D
+
BCP was significantly lower for live
B. abortus
2308-infected cells than for either
Brucella
mutant strains or control particles.
B. abortus
2308 persisted within these cathepsin D
−
, LAMP-1
+
, and acidic vesicles; however, at the onset of intracellular replication, the numbers of acidic
B. abortus
2308 BCP decreased while remaining cathepsin D
−
and LAMP-1
+
. In contrast to
B. abortus
2308, the isogenic
hfq
and
bacA
mutants remained in acidic, LAMP-1
+
phagosomes and failed to initiate intracellular replication. Notably, markers specific for the host endoplasmic reticulum were absent from the BCPs throughout the course of the infection. Thus, opsonized
B. abortus
in human monocytes survives within phagosomes that remain in the endosomal pathway and replication of virulent
B. abortus
2308 within these vesicles corresponds with an increase in intraphagosomal pH.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
65 articles.
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