TY - JOUR
T1 - Reduced expression of gamma interferon in serum and marked lymphoid depletion induced by Porphyromonas gingivalis increase murine morbidity and mortality due to cytomegalovirus infection
AU - Stern, Jacob
AU - Shai, Ela
AU - Zaks, Batia
AU - Halabi, Amal
AU - Houri-Haddad, Yael
AU - Shapira, Lior
AU - Palmon, Aaron
N1 - Funding Information:
WAF: Has received speaker fees, and educational and unrestricted research grants from Merck Canada.
Funding Information:
The work was partially supported by public grants from the European Commission (7th Framework Programme grants HEALTH-F3-2010-242061, PREHDICT and HEALTH-F2-2011-282562, HPV AHEAD), from the Instituto de Salud Carlos III (Spanish Government) (grants FIS PI08/1535, FIS PI10/02995, FIS PI11/02090, FIS PI11/02096, FIS PI11/02104, RCESP C03/09, RTICESP C03/10, RTIC RD06/0020/0095, RD12/0036/0056 and CIBERESP) and from the Agència de Gestió d’Ajuts Universitaris i de Recerca – Generalitat de Catalunya (Catalonian Government) (grants AGAUR 2005SGR00695 and AGAUR 2009SGR126), who had no role in data collection, analysis or interpretation of results. Thomas R. Broker receives research support from the USPHS/NIH/National Cancer Institute (grants “Human Papillomavirus Gene Expression” CA36200 and “Mechanisms of Human Papillomavirus DNA Replication” CA83679). Anna-Barbara Moscicki's work is supported by US Public Health Service grant R37 CA51323 (National Cancer Institute, National Institutes of Health, Department of Health and Human Services) and National Institute of AIDS and Infectious Disease RC1 AI86051. John Doorbar is funded by the UK Medical Research Council through program grant MC_U117584278 (Molecular Biology of Human Papillomavirus Infection). Marc Arbyn received financial support from: (1) the 7th Framework Programme of DG Research of the European Commission through the PREHDICT project (grant No. 242061, coordinated by the Vrije Universiteit Amsterdam, the Netherlands) and through the HPV AHEAD Network (FP7-HEALTH-2011-282562); (2) the Belgian Foundation Against Cancer (Brussels, Belgium); and (3) the International Agency for Research on Cancer (Lyon, France). Jack Cuzick was supported in part by Cancer Research UK programme grant A10404. Karen Canfell is supported by grants from the National Health and Medical Research Council, Australia (CDF APP1007994 and Project Grant #1007518), by non-commercial government and academic consulting agreements in Australia, New Zealand and the UK, and by Cancer Council NSW, Australia. Lynette A. Denny was partially supported by Bill and Melinda Gates Foundation, USA (35537). The work of Chris J.L.M. Meijer received support via the 7 th Framework Programme of DG Research of the European commission through the PREHDICT project (grant 242061, coordinated via the Vrije Universiteit Amsterdam). Jane J. Kim is supported in part by grants from the U.S. National Cancer Institute (U54 CA164336, R01 CA160744-01A1) and the Bill and Melinda Gates Foundation (30505) for modeling of HPV and cervical cancer in developing countries.
Funding Information:
JD: Is supported by the UK Medical Research Council, has recently acted as consultant for Sanofi Pasteur MSD, Merck and Roche, and has received research support from Sanofi Pasteur MSD, GlaxoSmithKline and the Wellcome Trust.
PY - 2004/10
Y1 - 2004/10
N2 - Porphyromonas gingivalis, a gram-negative anaerobe, is a major etiological agent of severe forms of periodontal disease. Although periodontal disease is considered a localized disease, accumulating evidence indicates that it may lead to a predisposition to a decline in immunocompetence. Human cytomegalovinis (CMV) commonly infects all human populations without producing significant clinical symptoms. Immunocompromised patients usually develop a primary or reactivated CMV infection, which is associated with high rates of morbidity and mortality. The aim of this study was to determine whether P. gingivalis increases animal susceptibility to CMV infection. Mice were inoculated with CMV and infected locally with P. gingivalis 3 days after the virus inoculation. Mortality rates were monitored, and traces of viral DNA and bacterial infection were detected systemically by using real-time PCR. Local and systemic cytokine secretion was measured, and histological sections were used to assess the pathological state of infected organs. P. gingivalis- and CMV-coinfected mice showed dramatically higher mortality rates than mice infected with P. gingivalis or CMV only. Although the organs of coinfected mice exhibited decreased viral titers, distinct necrosis and tissue damage were more evident in the livers and spleens of these mice than in those of mice infected with CMV only. Furthermore, systemic gamma interferon levels were decreased in coinfected mice, and marked lymphoid depletion was observed in their necrotic organs. In parallel control Escherichia coli-CMV coinfection experiments, the mortality and pathological results were the same as those found in mice infected with CMV only. Our results suggest a specific influence of P. gingivalis on the mouse immune response, causing increased susceptibility to CMV infection.
AB - Porphyromonas gingivalis, a gram-negative anaerobe, is a major etiological agent of severe forms of periodontal disease. Although periodontal disease is considered a localized disease, accumulating evidence indicates that it may lead to a predisposition to a decline in immunocompetence. Human cytomegalovinis (CMV) commonly infects all human populations without producing significant clinical symptoms. Immunocompromised patients usually develop a primary or reactivated CMV infection, which is associated with high rates of morbidity and mortality. The aim of this study was to determine whether P. gingivalis increases animal susceptibility to CMV infection. Mice were inoculated with CMV and infected locally with P. gingivalis 3 days after the virus inoculation. Mortality rates were monitored, and traces of viral DNA and bacterial infection were detected systemically by using real-time PCR. Local and systemic cytokine secretion was measured, and histological sections were used to assess the pathological state of infected organs. P. gingivalis- and CMV-coinfected mice showed dramatically higher mortality rates than mice infected with P. gingivalis or CMV only. Although the organs of coinfected mice exhibited decreased viral titers, distinct necrosis and tissue damage were more evident in the livers and spleens of these mice than in those of mice infected with CMV only. Furthermore, systemic gamma interferon levels were decreased in coinfected mice, and marked lymphoid depletion was observed in their necrotic organs. In parallel control Escherichia coli-CMV coinfection experiments, the mortality and pathological results were the same as those found in mice infected with CMV only. Our results suggest a specific influence of P. gingivalis on the mouse immune response, causing increased susceptibility to CMV infection.
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U2 - 10.1128/IAI.72.10.5791-5798.2004
DO - 10.1128/IAI.72.10.5791-5798.2004
M3 - Article
C2 - 15385479
AN - SCOPUS:4644318032
SN - 0019-9567
VL - 72
SP - 5791
EP - 5798
JO - Infection and Immunity
JF - Infection and Immunity
IS - 10
ER -