Therapeutic potential of the immunomodulatory proteins Wuchereria bancrofti L2 and Brugia malayi abundant larval transcript 2 against streptozotocin-induced type 1 diabetes in mice

Abstract

Epidemiological and experimental evidence has supported the concept of using helminths as alternative bio-therapeutic agents in the treatment of type 1 diabetes (T1D). In the current study, two filarial proteins, recombinant Wuchereria bancrofti L2 (rWbL2) and Brugia malayi abundant larval transcript 2 (rBmALT-2) have been investigated, individually and in combination, for their therapeutic potential in streptozotocin (STZ)-induced T1D. The rWbL2 and rBmALT-2 proteins, when administered individually or in combination, have resulted in lowering of the blood glucose levels and reducing the incidence of T1D in mice. In addition, these proteins have led to reduced lymphocytic infiltration and decreased islet damage and inflammation. The curative effect was found to be associated with the suppression of release of tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), and increased production of interleukin (IL)-4, IL-5 and IL-10 cytokines by the splenocytes of the diabetic mice. Insulin-specific IgG1 and antigen-specific IgE antibodies were found to be elevated in the sera of mice treated with rWbL2 and rBmALT-2 proteins. From the findings in this study, it can be envisaged that both of these filarial immunomodulatory proteins have the potential to ameliorate T1D by altering the regulatory immune responses.

SXP–RAL Family Filarial Protein, rWbL2, Prevents Development of DSS-Induced Acute Ulcerative Colitis

“…In our study after treatment with rWbL2, increased levels of the expression of anti-inflammatory cytokine IL-10 and decreased levels of expression of proinflammatory cytokines such as IFN-c, TNF-a, IL-6 and IL-17a was found. This protein has already shown to have immunomodulatory activity through alteration of cytokine levels [14]. This study demonstrated that such alteration in cytokine levels might be directly associated with change in gene expression.…”

“…Therefore, this study has been undertaken to assess the preventive effect of a purified secretory filarial protein rWbL2 against inflammatory ulcerative colitis disease. rWbL2 is one of the secretory SXP/RAL family of proteins [14]. Increased rWbL2 specific IgG4 antibody levels was reported in the sera of actively infected individuals (Shivprasad B unpublished data), which is consistently associated with the increased secretion of IL-10 [13].…”

“…For the validation of therapeutic responses and utilization of immunomodulators, understanding of mechanism of action, of rWbL2, in terms of cellular and humoral immune responses is necessary. For this purpose, splenocytes from the treated mice were stimulated with 10 lg/mL of rWbL2 for 48 h (pre-optimized condition) [14,17,29]. Following this treatment, anti-inflammatory and pro-inflammatory gene expression analysis was performed.…”

“…Filarial protein rWbL2 was prepared as described earlier using Escherichia coli (E. coli) based expression system [14]. Briefly, pRSETA-Wbl2 plasmid was constructed, transformed into BL21 (DE3) pLysS Escherichia coli expression host and expressed as His-tag proteins by inducing with 1 mM isopropyl b-D-1-thiogalactopyranoside (Merck Millipore, Bangalore, India).…”

Human filarial proteins attenuate chronic colitis in an experimental mouse model

“…In those patients, the continuous inflammation destroys mucosal epithelia causing chronic stage of UC. Hence, in this study, three selected filarial recombinant molecules (namely rBmCys, rBmALT2 and rWbL2), with pronounced therapeutic effect in various immune‐mediated disorders, were assessed individually or in combinations for their therapeutic activity on chronic colitis.…”