Impact of hepcidin antimicrobial peptide on iron overload in tuberculosis patients

Background: Iron acquisition is essential for the growth of Mycobacterium tuberculosis. Hepcidin is known as an antimicrobial peptide and a component of the innate immune response. Hepcidin inhibits M. tuberculosis growth in vitro. In this study, we decided to identify-582A> G variants of the HAMP promoter in patients with tuberculosis (TB) and investigate its effect on serum iron, ferritin, and hepcidin levels. Methods: The sample population consisted of 105 patients with TB and 104 healthy individuals. The-582A> G polymorphism was genotyped using a tetra-primers PCR set. Serum levels of hepcidin were determined using an ELISA kit. Statistical analysis was performed using SPSS software. Results: The G allele is meaningfully associated with TB disease (95% confidence interval = 2-4.8, p G polymorphism genotypes. There was significant reverse correlation between hepcidin and iron (r =-0.849, p = 0.006). Conclusion: A high association was found between serum hepcidin levels and the HAMP-582A> G variants in patients with TB. These observations indicate a hypothetical role of this polymorphism in iron metabolism. Hepcidin could perhaps be an option for the treatment of TB. © 2014 Informa Healthcare

Host Antimicrobial Peptides: the promise of new treatment strategies against Tuberculosis

Tuberculosis (TB) continues to be a devastating infectious disease and remerges as a global health emergency due to an alarming rise of antimicrobial resistance to its treatment. Despite of the serious effort that has been applied to develop effective antitubercular chemotherapies, the potential of antimicrobial peptides (AMPs) remains underexploited. A large amount of literature is now accessible on the AMP mechanisms of action against a diversity of pathogens; nevertheless, research on their activity on mycobacteria is still scarce. In particular, there is an urgent need to integrate all available interdisciplinary strategies to eradicate extensively drug-resistant Mycobacterium tuberculosis strains. In this context, we should not underestimate our endogenous antimicrobial proteins and peptides as ancient players of the human host defense system. We are confident that novel antibiotics based on human AMPs displaying a rapid and multifaceted mechanism, with reduced toxicity, should significantly contribute to reverse the tide of antimycobacterial drug resistance. In this review, we have provided an up to date perspective of the current research on AMPs to be applied in the fight against TB. A better understanding on the mechanisms of action of human endogenous peptides should ensure the basis for the best guided design of novel antitubercular chemotherapeutics

Myeloid-derived suppressor cells in B cell malignancies

Tumor cells use several mechanisms such as soluble immune modulators or suppressive immune cells to evade from anti-tumor responses. Immunomodulatory cytokines, such as transforming growth factor-beta, interleukin (IL)-10, and IL-35, soluble factors, such as adenosine, immunosuppressive cells, such as regulatory T cells, NKT cells and myeloid-derived suppressor cells (MDSCs), are the main orchestra leaders involved in immune suppression in cancer by which tumor cells can freely expand without immune cell-mediated interference. Among them, MDSCs have attracted much attention as they represent a heterogenous population derived from myeloid progenitors that are expanded in tumor condition and can also shift toward other myeloid cells, such as macrophages and dendritic cells, after tumor clearing. MDSCs exert their immunosuppressive effects through various immune and non-immune mechanisms which make them as potent tumor-promoting cells. Although, there are several studies regarding the immunobiology of MDSCs in different solid tumors, little is known about the precise characteristics of these cells in hematological malignancies, particularly B cell malignancies. In this review, we tried to clarify the precise role of MDSCs in B cell-derived malignancies