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Acute dehydrating disease caused by Vibrio cholerae serogroups O1 and O139 induce increases in innate cells and inflammatory mediators at the mucosal surface of the gut

F Qadri¹, T R Bhuiyan¹, K K Dutta¹, R Raqib¹, M S Alam¹, N H Alam¹, A-M Svennerholm², M M Mathan¹

¹ International Centre for Diarrhoeal Disease Research, Bangladesh, GPO Box 128, Dhaka 1000, Bangladesh
² Department of Medical Microbiology and Immunology, Göteborg University, Guldhedsgatan 10, S-413 46 Göteborg, Sweden

Correspondence to:
Correspondence to:
Dr F Qadri
Laboratory Sciences Division, ICDDR,B, GPO Box 128, Dhaka 1000, Bangladesh; fqadri{at}icddrb.org

Background and aims: The general concept is that as Vibrio cholerae is not invasive, it mediates a non-inflammatory type of infection. This is being re-evaluated based on available data that natural cholera infection or cholera toxin induces a Th2-type of immune profile and stimulates the humoral immune response, innate cells, and mediators in the host.

Methods: To perform a comprehensive analyses of the inflammatory components, we studied mucosal biopsies from patients, both adults and children with acute watery diarrhoea caused by V cholerae O1 and O139. Patients with cholera, adults (n = 30) and children (n = 18), as well as healthy controls (n = 24) were studied. Histochemical, immunohistochemical, and ultrastructural studies were carried out to elucidate the contribution of the different factors using paraffin and frozen duodenal and/or rectal sections as appropriate. Samples were collected during the acute stage and during early and/or late convalescence.

Results: Following natural cholera infection, patients responded with increases in neutrophil polymorphs during the acute stage (p<0.001) compared with healthy controls whereas mucosal mast cells (MMC) (p = 0.008) and eosinophils (p = 0.034) increased in the gut during convalescence. Electron microscopic analyses of duodenal biopsies from adult patients showed increased piecemeal degranulation in both MMC and eosinophils and accumulation of lipid bodies in MMC. Duodenal biopsies from V cholerae O1 infected patients showed upregulation of myeloperoxidase, lactoferrin, PGHS-1, SCF, tryptase, tumour necrosis factor , -defensin, and eotaxin during the acute stage and chymase, interleukin 3 and major basic protein during convalescence.

Conclusion: We have shown that innate cells and their mediators are upregulated in acute watery diarrhoea. These cells and factors of the innate arm may be important in the host’s defence against cholera. Such effects may need to be simulated in a vaccine to achieve long lasting protection from cholera.

Keywords: cholera; polymorphonuclear neutrophil; eosinophil; mucosal mast cell; mediators

Abbreviations: MMC, mucosal mast cell; PMN, polymorphonuclear neutrophil; LP, lamina propria; PMD, piecemeal degranulation; AND, anaphylactic degranulation; MBP, major basic protein; TNF-, tumour necrosis factor ; IL, interleukin; MPO, myeloperoxidase; CCR3, chemokine receptor 3; LT, leukotrienes; PGHS-1, prostaglandin H synthase 1; SCF, stem cell factor

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