Role of IL-10 Deficiency in Pneumonia Induced by Corynebacterium kutscheri in Mice
ABSTRACT IL-10 is an important anti-inflammatory cytokine that can inhibit the production of many pro-inflammatory cytokines. Both human and animal studies have shown that pro-inflammatory cytokines play an important role in pneumonia and other inflammatory lung diseases. In the present study, IL-10 knockout (KO) and wild-type mice were infected with Corynebacterium kutscheri to determine whether the severity of pathogenesis and whether protective immunity could be altered in the absence of IL- 10. The survival rate was significantly lower in IL-10 KO mice than wild-type mice. The number of neutrophils in bronchoalveolar lavage fluid and blood were found to be higher in IL-10 KO mice than wild-type mice. IL-10 KO mice showed greater neutrophil infiltration, excessive inflammation, and weight-loss compared with wild-type mice. Furthermore, upregulation of IFN-gamma in bronchoalveolar lavage fluid, and upregulation of MIP-1alpha and IP-10 mRNA in the lungs of IL-10 KO mice compared with wild-type mice after C. kutscheri infection were observed. These results suggest that IL-10 plays an important role in the anti-inflammatory properties against C. kutscheri infection, and that lack of IL-10 leads to a more severe pulmonary inflammatory response. This increased susceptibility to C. kutscheri pneumonia is at least in part caused by IL-10 deficiency and severe recruitment of neutrophils.
SourceAvailable from: Peter H Nibbering[Show abstract] [Hide abstract]
ABSTRACT: Despite many reports documenting its epidemicity, little is known on the interaction of Acinetobacter baumannii with its host. To deepen our insight into this relationship, we studied persistence of and host response to different A. baumannii strains including representatives of the European (EU) clones I-III in a mouse pneumonia model. Neutropenic mice were inoculated intratracheally with five A. baumannii strains and an A. junii strain and at several days morbidity, mortality, bacterial counts, airway inflammation, and chemo- and cytokine production in lungs and blood were determined. A. baumannii RUH875 and RUH134 (EU clone I and II, respectively) and sporadic strain LUH8326 resulted in high morbidity/mortality, whereas A. baumannii LUH5875 (EU clone III, which is less widespread than clone I and II) caused less symptoms. A. baumannii type strain RUH3023(T) and A. junii LUH5851 did not cause disease. All strains, except A. baumannii RUH3023(T) and A. junii LUH5851, survived and multiplied in the lungs for several days. Morbidity and mortality were associated with the severity of lung pathology and a specific immune response characterized by low levels of anti-inflammatory (IL-10) and specific pro-inflammatory (IL-12p40 and IL-23) cytokines at the first day of infection. Altogether, a striking difference in behaviour among the A. baumannii strains was observed with the clone I and II strains being most virulent, whereas the A. baumannii type strain, which is frequently used in virulence studies appeared harmless.PLoS ONE 02/2012; 7(2):e30673. DOI:10.1371/journal.pone.0030673 · 3.53 Impact Factor
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ABSTRACT: Interleukin (IL)-10 is an anti-inflammatory cytokine that modulates sepsis by decreasing pro-inflammatory cytokine production and chemokine expression. In this study, IL-10-deficient and wild-type (WT) mice were infected with Corynebacterium kutscheri to determine if the absence of IL-10 altered the protective immunity and pathogenesis. After infection, IL-10 knockout (KO) mice had a higher survival rate than WT mice. The decrease of body weight and the increased weight of organs such as liver and spleen were greater in WT mice. Bacterial counts were significantly increased after inoculation in WT mice over those in IL-10 KO mice. WT mice had more granulomatous inflammation and coagulative necrosis in the liver and spleen, lymphocyte depletion in lymphoid follicles, and apoptosis of immune cells in the spleen. WT mice had significantly higher plasma concentrations of aspartate aminotransferase and alanine aminotransferase. Furthermore, more upregulation of tumor necrosis factor-α and IL-4 in the plasma, macrophage inflammatory protein-2, keratinocyte-derived chemokine, inducible nitric oxide synthase, and interferon-inducible protein 10 mRNA in the spleen were observed in WT mice after inoculation. These results suggest that the lack of IL-10 contributes to an increase in the systemic clearance of C. kutscheri, and that IL-10 plays a detrimental role in controlling systemic C. kutscheri infection.The Journal of Microbiology 04/2012; 50(2):301-10. DOI:10.1007/s12275-012-1298-z · 1.53 Impact Factor
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ABSTRACT: Background and objectiveThe mechanisms of Mycoplasma pneumoniae induced lung inflammation are not clearly understood yet. This study investigated whether activated T cells in the airway contributed to the pulmonary inflammation in patients with severe Mycoplasma pneumoniae pneumonia (MPP).MethodsBALF were collected in all 45 patients with MPP (MPP, n = 45), including mild (Mild, n = 20) and severe (Severe, n = 25) group. BALF in 20 of all 25 severe cases with MPP at the recovery stage (Rec-severe, n = 20) were collected again. The control group consisted of 20 patients with airway foreign body aspiration (Con., n = 20). CD3+ T cells, CD69+, HLA-DR+, CD25+ on CD3+ T cells in BALF were determined by flow cytometry. Levels of IL-6, IL-10 in BALF were determined by ELISA, and percentage of neutrophils was counted.ResultsA significant increased percentage of neutrophils and levels of IL-6 and IL-10, decreased percentage of CD3+ T cells, increased expressions of CD69+, HLA-DR+ or CD25+ on CD3+ T cells were observed in children with MPP compared with the control group (P < 0.05 or 0.01). Compared to mild group, the percentage of neutrophils, CD3+ CD25+, IL-6, and IL-10 were increased in children with severe MPP (P < 0.01 or 0.05). Compared to acute stage, an increased percentage of CD3+ T cells, decreased percentage of neutrophils and IL-6 level, and expressions of CD3+ CD69+ or CD3+ CD25+ were observed at the recovery stage in children with severe MPP (P < 0.01 or 0.05).Conclusions Increased activation of T cell in BALF may play an important role in the inflammatory response of acute and severe MPP. IL-6 may predict the severity and prognosis and provide a better assessment for patient care. However, the underlying mechanism awaits further detailed investigations. Pediatr Pulmonol. © 2014 Wiley Periodicals, Inc.Pediatric Pulmonology 08/2014; DOI:10.1002/ppul.23095 · 2.30 Impact Factor