HP-NAP

Helicobacter pylori is a Gram-negative bacterium that chronically infects the stomach of over 50% of the human population. It is a major cause of gastroduodenal pathologies, including peptic ulcers, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma . One of the key virulence factors of H. pylori is the Neutrophil-Activating Protein A (HP-NAP), which plays a significant role in the bacterium’s ability to modulate the host immune response .

HP-NAP is a dodecameric protein with a molecular weight of approximately 150 kDa. It has a structure similar to bacterioferritin, including a central cavity for iron accumulation . The protein was initially identified for its ability to promote the adhesion of neutrophils to endothelial cells and stimulate the production of reactive oxygen species (ROS) by neutrophils .

HP-NAP is a potent immune modulator. It attracts and activates neutrophils, promoting their endothelial adhesion and the production of oxygen radicals and chemokines such as CXCL8, CCL3, and CCL4 . HP-NAP acts as a TLR2 agonist, inducing the expression of interleukin-12 (IL-12) and IL-23 by human neutrophils and monocytes . This protein has the potential to shift antigen-specific T-cell responses from a Th2 to a Th1 cytotoxic phenotype, characterized by high levels of interferon-γ and tumor necrosis factor-α production .

HP-NAP is a key factor driving Th1 inflammation in H. pylori infection and may be a valuable tool for future therapeutic strategies aimed at redirecting Th2 into Th1 responses. This could be beneficial in conditions such as atopy, vaccinology, and cancer immunotherapy . Additionally, recombinant HP-NAP (rNAP) has shown promise in preventing allergic asthma in mice by reducing eosinophil accumulation and inflammatory infiltration in lung tissue .