http://qjmed.oxfordjournals.org/content/102/10/673.long
QJM. 2009 Oct;102(10):673-84. Epub 2009 Jun 25.
Q fever: persistence of antigenic non-viable cell residues of Coxiella
burnetii in the host=97implications for post Q fever infection fatigue
syndrome and other chronic sequelae
Marmion BP, Sukocheva O, Storm PA, Lockhart M, Turra M, Kok T, Ayres
J, Routledge H, Graves S.
Q fever Research Group, SA Pathology/Hanson Institute, Adelaide,
Australia. bpmarmion@iprimus.com.au
Abstract
Background: Our previous studies of persistence of Coxiella burnetii
in humans after an initial acute Q fever infection revealed raised,
maintained antibody levels and low levels of coxiella genomic DNA at
the age of 5 years from onset in Australian patients and at 12 years
in patients in the 1989 Birmingham UK Q fever outbreak. Attempts to
isolate the coxiella in standard cell culture and susceptible mice by
serial passage of PCR positive PBMC and bone marrow were negative.
Aim: To retest PCR positive patient samples by more sensitive methods
for viable coxiellas and for the coxiella cell components of antigen
and specific lipopolysaccharide (LPS). To re-interpret the previous
results in the light of the new information. To review the pertinent
literature for a concept of an immuno-modulatory complex generated by
the current studies.
Design: Laboratory case study.
Methods: Stored patient samples were inoculated into SCID mice that
were followed for 60 days. Mouse spleen and liver samples were then
examined by PCR assay for targets in the COM1 and IS1111a sequences
and for antigens by IFA with a polyclonal rabbit antiserum to C.
burnetii Phase 1 and a monoclonal antiserum to Phase 1 LPS (details;
O. Sukocheva et al., unpublished data).
Results: All specimens, including a recently excised heart valve from
a Birmingham patient with late developing endocarditis, were infection
negative in SCID mice. Dilutions of SCID mouse spleen and liver
homogenates titrated in PCR assays were negative at dilutions attained
by control mice inoculated with an endpoint dilution of a viable
prototype strain of C. burnetii. Sections of the spleens from all
specimens showed a complex of coxiella antigen-LPS by IFA.
Discussion/Review: We advance a concept of long-term persistence of a
non-infective, non-biodegraded complex of coxiella cell components
with its antigens and specific LPS [so called Immunomodulatory complex
(IMC)] associated with traces of genomic DNA that signalled its
presence in our earlier studies. The IMC's survival in patients for at
least 12 years, and in one patient for 70 years implies a capacity for
serial passage in macrophages with effective down-regulation of their
biodegrading functions. The review assesses the compatibility of the
IMC concept in relation to cogent literature on C. burnetii
interactions with macrophage and cell-mediated immunity. Some
remaining gaps in our knowledge of the organ sites and duration of
carriage of viable coxiellas after initial infection are also
identified.
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