TY - JOUR AB - Airway mucins are the major molecular constituents of mucus. Mucus forms the first barrier to invading organisms in the airways and is an important defense mechanism of the lung. We confirm that mucin concentrations are significantly decreased in airway secretions of subjects with cystic fibrosis (CF) who have chronic Pseudomonas aeruginosa (PA) infection. In sputum from CF subjects without a history of PA, we found no significant difference in the mucin concentration compared to mucus from normal controls. We demonstrate that mucins can be degraded by synthetic human neutrophil elastase (HNE) and PA-elastase-B (pseudolysin) and that degradation was inhibited by the serine proteases inhibitors (diisopropyl fluorophosphates (DFP), phenylmethyl sulfonyl fluoride (PMSF), and 1-chloro-3-tosylamido-7-amino-2-heptanone HCl (TLCK)). The mucin concentration in airway secretions from CF subjects is similar to normal subjects until there is infection by PA, and after that, the mucin concentration decreases dramatically. This is most likely due to degradation by serine proteases. The loss of this mucin barrier may contribute to chronic airway infection in the CF airway. AU - Henke, M.O.* AU - John, G. AU - Rheineck, C.* AU - Chillappagari, S.* AU - Naehrlich, L.* AU - Rubin, B.K. C1 - 5652 C2 - 28583 SP - 3438-3444 TI - Serine proteases degrade airway mucins in cystic fibrosis. JO - Infect. Immun. VL - 79 IS - 8 PB - American Society for Microbiology PY - 2011 SN - 0019-9567 ER - TY - JOUR AB - Trypanosoma congolense is a protozoan parasite that causes severe diseases in livestock. Three major quantative trait loci (QTL), Tir1, Tir2, and Tir3, control the survival time of mice after infection with T. congolense. Congenic mice carrying the C57BL/6 resistance alleles on the A/J background were developed for each of these loci. The congenic mice were used to physically map the regions containing the QTL gene(s) and to investigate the physiological effect of each locus. Clinical chemistry data for infected A/J, C57BL/6, and BALB/c mice were obtained for 15 analytes at five time points. Congenic mice were assessed for survival, parasitemia, and anemia as well as seven clinical-chemical analytes. The survival times were significantly increased in the Tir1 and Tir2 mice but not Tir3 congenic mice. The survival time of the parental inbred mice correlated negatively with parasitemia but positively with alanine aminotransferase activities in serum, suggesting that inflammatory reactions in the liver had a beneficial effect possibly associated with reduced parasitemia. However, there was no difference in parasitemia or liver enzyme activities of Tir1 and Tir2 congenic mice relative to their controls, showing that survival, parasitemia, and degree of liver damage are not associated with each other, despite the correlation in the parental lines. These data suggest that the congenic loci affect survival but do not affect control of parasite number. They may therefore act by limiting the pathological consequences of T. congolense infection. AU - Rathkolb, B. AU - Noyes, H.A.* AU - Brass, A.* AU - Dark, P.* AU - Fuchs, H. AU - Gailus-Durner, V. AU - Gibson, J.* AU - Hrabě de Angelis, M. AU - Ogugo, M.* AU - Iraqi, F.* AU - Kemp, S.J.* AU - Naessens, J.* AU - Pope, M.E.* AU - Wolf, E.* AU - Agaba, M.* C1 - 1094 C2 - 26435 CY - Washington SP - 3948-3957 TI - Clinical chemistry of congenic mice with quantitative trait loci for predicted responses to Trypanosoma congolense infection. JO - Infect. Immun. VL - 77 IS - 9 PB - Amer Soc Microbiology PY - 2009 SN - 0019-9567 ER - TY - JOUR AB - The induction of proinflammatory cytokines such as gamma interferon (IFN-gamma) and tumor necrosis factor alpha is crucial for the early control of bacterial infections. Since interleukin-18 (IL-18) acts as a potent inducer of IFN-gamma, it might play an important role in the induction of a protective immune response in listeriosis. We used a murine model of systemic Listeria monocytogenes infection to study the immune response to these intracellular bacteria in the absence of IL-18. For this purpose, IL-18-deficient mice and mice treated with anti-IL-18 neutralizing antibody were infected with L. monocytogenes, and their innate and adaptive immune responses were compared to those of control mice. Unexpectedly, we found that mice deficient in IL-18 were partially resistant to primary infection with L. monocytogenes. At day 3 after infection, the numbers of listeriae in the livers and spleens of control mice were up to 500 times higher than those in IL-18-deficient or anti-IL-18 antibody-treated mice. In addition, the level of proinflammatory cytokines was markedly reduced in IL-18-deficient mice. Enhanced resistance to L. monocytogenes infection in IL-18-deficient mice was accompanied by increased numbers of leukocytes and reduced apoptosis in the spleen 48 to 72 h after infection. In contrast, control and IL-18-deficient mice showed no significant differences in their abilities to mount a protective L. monocytogenes-specific T-cell response. AU - Lochner, M.* AU - Kastenmüller, K. AU - Neuenhahn, M.* AU - Weighardt, H.* AU - Busch, D.H. AU - Reindl, W.* AU - Förster, I.* C1 - 3543 C2 - 25606 SP - 3881-3890 TI - Decreased susceptibility of mice to infection with Listeria monocytogenes in the absence of interleukin-18. JO - Infect. Immun. VL - 76 IS - 9 PB - Amer. Soc. Microbiology PY - 2008 SN - 0019-9567 ER - TY - JOUR AU - Kufer, T.A.* AU - Kremmer, E. AU - Banks, D.J.* AU - Philpott, D.J.* C1 - 4932 C2 - 23893 SP - 3115-3124 TI - Role for Erbin in bacterial activation of Nod2. JO - Infect. Immun. VL - 74 PY - 2006 SN - 0019-9567 ER - TY - JOUR AB - It is well documented that sex-dependent factors affect susceptibility to infection, with most mouse models demonstrating higher resistance in females. We made the unexpected observation that infection with the intracellular bacterium Listeria monocytogenes showed an opposite pattern in several commonly used inbred mouse strains: female C57BL/6J, BALB/c, C3H/HeN, and CBA/J mice were significantly more susceptible to Listeria infection. The pronounced sensitivity of females to Listeria, which was revealed by significantly higher lethality rates, correlated also with increased bacterial numbers in organ tissues (spleen and liver) and several immunological changes in peripheral blood samples. Surprisingly, increased severity of infection in females was associated with elevated interleukin-10 (IL-10) levels in plasma. Experiments using Il10 knockout mice, for which no differences between the susceptibilities of males and females to Listeria infection could be detected, confirmed the important role of this immunosuppressive cytokine for the outcome of disease. Our findings are likely to have clinical relevance, since similar sex differences with regard to infection with Listeria monocytogenes and other intracellular pathogens have been reported for humans. AU - Pasche, B.* AU - Kalaydjiev, S.* AU - Franz, T.J.* AU - Kremmer, E. AU - Gailus-Durner, V. AU - Fuchs, H. AU - Hrabě de Angelis, M. AU - Lengeling, A.* AU - Busch, D.H.* C1 - 3284 C2 - 22861 SP - 5952-5960 TI - Sex-dependent susceptibility to Listeria monocytogenes infection is mediated by differential interleukin-10 production. JO - Infect. Immun. VL - 73 IS - 9 PY - 2005 SN - 0019-9567 ER - TY - JOUR AU - Barthel, M.* AU - Hapfelmeier, S.* AU - Quintanilla-Martinez, L. AU - Kremer, M. AU - Rohde, M.* AU - Hogardt, M.* AU - Pfeffer, K.* AU - Rüssmann, H.* AU - Hardt, W.-D.* C1 - 9652 C2 - 20975 SP - 2839-2858 TI - Pretreatment of Mice with Streptomycin a Salmonella enterica Serovar Typhimurium Colitis Model that Allows Analysis of Both Pathogen and Host. JO - Infect. Immun. VL - 71 PY - 2003 SN - 0019-9567 ER - TY - JOUR AU - Barthel, M.* AU - Hapfelmeier, S.* AU - Quintanilla-Martinez, L. AU - Kremer, M. AU - Rohde, M.* AU - Hogardt, M.* AU - Pfeffer, K.* AU - Rüssmann, H.* AU - Hardt, W.-D.* C1 - 22293 C2 - 21098 SP - 2839-2858 TI - Pretreatment of Mice with Streptomycin Provides a Salmonella enterica Serovar Typhimurium Colitis Model that Allows Analysis of Both Pathogen and Host. JO - Infect. Immun. VL - 71 PY - 2003 SN - 0019-9567 ER - TY - JOUR AU - Stassen, M.* AU - Müller, C.* AU - Richter, C.* AU - Neudörfl, C.* AU - Hültner, L. AU - Bhakdi, S.* AU - Walev, I.* AU - Schmitt, E.* C1 - 9520 C2 - 21311 SP - 6171-6177 TI - The Streptococcal Exotoxin Streptolysin O Activates Mast Cells to Produce Tumor Necrosis Factor Alpha by p38 Mitogen-Activated Protein Kinase- and Protein Kinase C-Dependent Pathways. JO - Infect. Immun. VL - 71 PY - 2003 SN - 0019-9567 ER - TY - JOUR AB - Langerhans cells (LC) take up Leishmania major and are critical for the induction of the parasite-specific T-cell response. Their functional activities are regulated by cytokines. We analyzed whether infection of LC with L. major modulates the expression of their cytokine receptors. The expression of the interleukin 4 (IL-4) receptor was increased on infected LC from susceptible mice but not on those from resistant mice. Moreover, IL-4 treatment strongly decreased the lipopolysaccharide-induced IL-12 response of infected LC from susceptible mice. This modulation of IL-4 receptor expression and IL-12 production by infection of LC with Leishmania may contribute to the development of Th2 cells and to susceptibility to infection. AU - Moll, H.* AU - Scharner, A. AU - Kämpgen, E.* C1 - 9651 C2 - 20362 SP - 1627-1630 TI - Increased Interleukin 4 (IL-4) Receptor Expression and IL-4-Induced Decrease in IL-12 Production by Langerhans Cells Infected with Leishmania major. JO - Infect. Immun. VL - 70 PB - Society PY - 2002 SN - 0019-9567 ER -