Systemic antibodies towards mucosal bacteria in ulcerative colitis and Crohn's disease differentially activate the innate immune response

Abstract

Background and aims: The mucosa in ulcerative colitis (UC) is replete with antibody producing plasma B cells and polymorphonuclear leucocytes (PMN). This combination of effector cells requires a crosslinking antigen to evoke an antibody driven PMN inflammatory response via their Fc receptors. The stimulus for activation is thought to be commensal bacteria colonising the gut mucosa. The aim of this investigation was to compare the principal culturable bacterial populations on the rectal mucosa of UC patients, and to determine whether specific antibodies towards these bacteria can activate infiltrating PMN through opsonisation. This would provide an explanation for this chronic inflammatory condition. Methods: Bacteria colonising rectal tissue were characterised using chemotaxonomic techniques. Systemic antibody responses were measured against total antigens and surface antigens of these organisms in UC and Crohn's disease (CD) patients, together with healthy controls. Antibody enhancement of the respiratory burst in PMN was also investigated, against a range of mucosal isolates. Results: Distinct differences were observed in some bacterial populations in UC biopsies, which were generally reflected in antibody responses towards these organisms. UC patients had higher IgG responses to surface antigens, primarily IgG1, whereas the response in CD was mainly IgG2. Antibodies from UC patients greatly enhanced the respiratory burst in PMN, in response to individual bacterial species. Conclusions: Changes in mucosal bacteria, and a switch from internal to surface antigen/antibody reactivity of a predominantly IgG1 type, leads to greater opsonisation of the respiratory burst in PMN, providing a mechanism for maintaining the inflammatory state in UC.

Extracellular proteins secreted by probiotic bacteria as mediators of effects that promote mucosa–bacteria interactions

“…In this context, the existence of antibodies directed against certain proteins secreted by the commensal microbiota in the framework of certain autoimmune diseases is known. Some examples of these proteins are porin OmpC from Escherichia coli, porin OmpW from Bacteroides caccae, protein I2 from Pseudomonas fluorescens and flagellin from Clostridium coccoides (Adams et al, 2008;Furrie et al, 2004;Iltanen et al, 2006;Müller et al, 2008). Theoretically, it is possible that certain extracellular proteins secreted by probiotic bacteria might also reach the gut mucosa, acting as molecular effectors responsible for downstream responses in mucosal cells.…”

Ursolic acid protects against ulcerative colitis via anti-inflammatory and antioxidant effects in mice

“…Ulcerative colitis, a type of inflammatory bowel disease, is characterized by uncontrolled inflammation in the colon and rectum, recurrent episodes of bloody diarrhea, cramping, abdominal pain, mucosal inflammation and injury (1). Considering the pathogenic mechanisms of ulcerative colitis, it is suggested that deregulation of the pro-/anti-inflammatory systems and antioxidant system may to be involved (2).…”

NCB-02 (standardized Curcumin preparation) protects dinitrochlorobenzene-induced colitis through down-regulation of NFκ-B and iNOS

“…Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis (UC), is a chronic and relapsing inflammatory disease caused by the inflammation and sores in the lining of large intestine and characterized clinically by recurrent episodes of bloody diarrhea, cramping, abdominal pain and histologically by mucosal inflammation and injury [1] . Conventional therapy for UC includes sulfasalazine and other 5-aminosalicylic acid (5-ASA) type of compounds, and in more persistent and/ or severe cases, oral, rectal and parenteral corticosteroids and immunosuppressants are administered [2] .…”