Combined exposure to cigarette smoke and nontypeable Haemophilus influenzae drives development of a COPD phenotype in mice

Abstract Background Cigarette smoke (CS) is the major etiologic factor of chronic obstructive pulmonary disease (COPD). CS-exposed mice develop emphysema and mild pulmonary inflammation but no airway obstruction, which is also a prominent feature of COPD. Therefore, CS may interact with other factors, particularly respiratory infections, in the pathogenesis of airway remodeling in COPD. Methods C57BL/6 mice were exposed to CS for 2 h a day, 5 days a week for 8 weeks. Mice were also exposed to heat-killed non-typeable H. influenzae (HK-NTHi) on days 7 and 21. One day after the last exposure to CS, mice were sacrificed and lung inflammation and mechanics, emphysematous changes, and goblet cell metaplasia were assessed. Mice exposed to CS or HK-NTHi alone or room air served as controls. To determine the susceptibility to viral infections, we also challenged these mice with rhinovirus (RV). Results Unlike mice exposed to CS or HK-NTHi alone, animals exposed to CS/HK-NTHi developed emphysema, lung inflammation and goblet cell metaplasia in both large and small airways. CS/HK-NTHi-exposed mice also expressed increased levels of mucin genes and cytokines compared to mice in other groups. CS/HK-NTHi-exposed mice infected with RV demonstrated increased viral persistence, sustained neutrophilia, and further increments in mucin gene and chemokine expression compared to other groups. Conclusions These findings indicate that in addition to CS, bacteria may also contribute to development of COPD, particularly changes in airways. Mice exposed to CS/HK-NTHi are also more susceptible to subsequent viral infection than mice exposed to either CS or HK-NTHi alone.http://deepblue.lib.umich.edu/bitstream/2027.42/109487/1/12931_2013_Article_1465.pd

Combined exposure to cigarette smoke and nontypeable Haemophilus influenzae drives development of a COPD phenotype in mice

Abstract Background Cigarette smoke (CS) is the major etiologic factor of chronic obstructive pulmonary disease (COPD). CS-exposed mice develop emphysema and mild pulmonary inflammation but no airway obstruction, which is also a prominent feature of COPD. Therefore, CS may interact with other factors, particularly respiratory infections, in the pathogenesis of airway remodeling in COPD. Methods C57BL/6 mice were exposed to CS for 2 h a day, 5 days a week for 8 weeks. Mice were also exposed to heat-killed non-typeable H. influenzae (HK-NTHi) on days 7 and 21. One day after the last exposure to CS, mice were sacrificed and lung inflammation and mechanics, emphysematous changes, and goblet cell metaplasia were assessed. Mice exposed to CS or HK-NTHi alone or room air served as controls. To determine the susceptibility to viral infections, we also challenged these mice with rhinovirus (RV). Results Unlike mice exposed to CS or HK-NTHi alone, animals exposed to CS/HK-NTHi developed emphysema, lung inflammation and goblet cell metaplasia in both large and small airways. CS/HK-NTHi-exposed mice also expressed increased levels of mucin genes and cytokines compared to mice in other groups. CS/HK-NTHi-exposed mice infected with RV demonstrated increased viral persistence, sustained neutrophilia, and further increments in mucin gene and chemokine expression compared to other groups. Conclusions These findings indicate that in addition to CS, bacteria may also contribute to development of COPD, particularly changes in airways. Mice exposed to CS/HK-NTHi are also more susceptible to subsequent viral infection than mice exposed to either CS or HK-NTHi alone.http://deepblue.lib.umich.edu/bitstream/2027.42/134587/1/12931_2013_Article_1465.pd

Extra-intestinal salmonellosis in a tertiary care centre in South India

Background and Objectives: Extra-intestinal salmonellosis is associated with higher case fatality and is underestimated in the developing countries like India. Here we present a case series of bacteriologically proven extra-intestinal salmonellosis managed at our institute over the past two years. Materials and Methods: Retrospective analysis of bacteriologically proven extra-intestinal salmonellosis over two years between January 2020 to December 2021 was carried out. Medical records were reviewed for site of infection, evidence of any underlying or predisposing illnesses and antimicrobial susceptibility report. Results: Eight patients were diagnosed with extra-intestinal salmonellosis. Male to female ratio was 3:1. Mean age was 44 years. Four were typhoidal and four were nontyphoidal Salmonellae. The extra-intestinal sites involved were purulent aspirates from scrotum, caecum, perianal region, intraperitoneal collection, synovium, and urine. Predisposing factors include chronic myeloid leukemia, HIV and gastric malignancy. All deep seated abscess required surgical intervention. All typhoidal Salmonella (n=4) were sensitive to cotrimoxazole, ampicillin, ceftriaxone. Among nontyphoidal Salmonella, one was resistant to cotrimoxazole; two were resistant to ampicillin, ceftriaxone and three resistant to ciprofloxacin. Conclusion: The diagnosis of extra-intestinal salmonellosis requires a high degree of clinical suspicion and should be included in the differential diagnosis in patients with deep-seated abscesses

Cable Pili and the Associated 22 Kda Adhesin Contribute to Burkholderia Cenocepacia Persistence In Vivo

Infection by Burkholderia cenocepacia in cystic fibrosis (CF) patients is associated with poor clinical prognosis. Previously, we demonstrated that one of the highly transmissible strains, BC7, expresses cable pili and the associated 22 kDa adhesin, both of which contribute to BC7 binding to airway epithelial cells. However, the contribution of these factors to induce inflammation and bacterial persistence in vivo is not known.Wild-type BC7 stimulated higher IL-8 responses than the BC7 cbl and BC7 adhA mutants in both CF and normal bronchial epithelial cells. To determine the role of cable pili and the associated adhesin, we characterized a mouse model of B. cenocepacia, where BC7 are suspended in Pseudomonas aeruginosa alginate. C57BL/6 mice were infected intratracheally with wild-type BC7 suspended in either alginate or PBS and were monitored for lung bacterial load and inflammation. Mice infected with BC7 suspended in PBS completely cleared the bacteria by 3 days and resolved the inflammation. In contrast, mice infected with BC7 suspended in alginate showed persistence of bacteria and moderate lung inflammation up to 5 days post-infection. Using this model, mice infected with the BC7 cbl and BC7 adhA mutants showed lower bacterial loads and mild inflammation compared to mice infected with wild-type BC7. Complementation of the BC7 cblS mutation in trans restored the capacity of this strain to persist in vivo. Immunolocalization of bacteria revealed wild-type BC7 in both airway lumen and alveoli, while the BC7 cbl and BC7 adhA mutants were found mainly in airway lumen and peribronchiolar region.B. cenocepacia suspended in alginate can be used to determine the capacity of bacteria to persist and cause lung inflammation in normal mice. Both cable pili and adhesin contribute to BC7-stimulated IL-8 response in vitro, and BC7 persistence and resultant inflammation in vivo

Lung MPO activity in BC7 infected C57BL/6 mice.

<p>Mice infected with BC7/PBS or BC7/alginate were sacrificed at specified times and MPO activity was determined in the lung homogenates. Data represents mean and SEM calculated from three independent experiments with a total of 6-7 mice per group (*different from respective uninfected group p≤0.05, †different from BC7/PBS group at respective time points p≤0.05, ANOVA).</p

Lung inflammation in C57BL/6 mice infected with BC7/PBS or BC7/alginate.

<p>Paraffin lung sections from mice infected with BC7/PBS (A, C, E and G) or BC7/alginate (B, D, F and H) were stained with H&E. A and B, 6 h post-infection; C and D, 1 d post-infection; E and F, 3 d post-infection; and G and H, 5 d post-infection, respectively. Insets in A, C, D, F and H represent magnified view of areas marked in respective panels and show infiltrated neutrophils. Images are representative of 3 individual animals at each time point.</p

Stimulation of IL-8 response by <i>B. cenocepacia</i> strains in airway epithelial cells.

<p>IB3 (A) or BEAS2B (B) cells were treated with media or media containing BC7, BC7 <i>adhA</i>, BC7 <i>cblA</i>, BC7 <i>cblS</i>, or the BC7 <i>cblS</i> complemented strain (BC7 <i>cblS</i> complement), and IL-8 was determined by ELISA. Data represents mean ± SEM calculated from three independent experiments carried out in triplicates. (*different from medium control, † different from BC7, #different from BC7 mutants p≤0.05, ANOVA).</p