Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Jun 29:13:944139.
doi: 10.3389/fimmu.2022.944139. eCollection 2022.

HP-NAP of Helicobacter pylori: The Power of the Immunomodulation

Gaia Codolo  1 , Sara Coletta  1 , Mario Milco D'Elios  2 , Marina de Bernard  1
Affiliations
Review

HP-NAP of Helicobacter pylori: The Power of the Immunomodulation

Gaia Codolo et al. Front Immunol. .

Abstract

The miniferritin HP-NAP of Helicobacter pylori was originally described as a neutrophil-activating protein because of the capacity to activate neutrophils to generate oxygen radicals and adhere to endothelia. Currently, the main feature for which HP-NAP is known is the ability to promote Th1 responses and revert the immune suppressive profile of macrophages. In this review, we discuss the immune modulating properties of the protein regarding the H. pylori infection and the evidence that support the potential clinical application of HP-NAP in allergy and cancer immunotherapy.

Keywords: HP-NAP; Helicobacter pylori; allergy; cancer; inflammation; therapy.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
HP-NAP activity in the context of H. pylori infection. Once released by H. pylori in the stomach lumen, HP-NAP crosses the gastric epithelial cell layer and the endothelium. Bound to the luminal face of the latter, it directly stimulates leukocytes to adhere and extravasate. In addition, HP-NAP activates recruited neutrophils and monocytes to secrete cytokines that further promote inflammation, and stimulates monocytes/macrophages and dendritic cells (antigen presenting cells, APC) to release of IL-12 which drives the differentiation of T helper cells towards the IFN-γ producing Th1 phenotype. Figure created with BioRender.com.
Figure 2
Figure 2
Immune modulating activities of HP-NAP applied to the treatment of allergy and cancer. (A) The delivery of pollen allergens to sub-epithelial APC that initiates the priming of T helper 2 (Th2) cells is a key step in the immunopathology of allergy. Treatment with HP-NAP stimulates APC to secrete IL-12 which mediate the skewing of Th2 lymphocytes towards a Th1 profile. This impacts on the allergic cascade and ameliorates the subsequent symptoms. (B) HP-NAP can potentiate weak natural Th1 responses, that per se are unable to exert protection against tumors (left) and shift the profile of macrophages from pro-oncogenic to pro-inflammatory and anti-tumoral (right). This results in a regression of tumor mass. Figure created with BioRender.com.
See this image and copyright information in PMC

References

    1. Andrews SC. “Iron Storage in Bacteria”. In: Advances in Microbial Physiology. (Amsterdam: Elsevier; ) (1998). p. 281–351. doi: 10.1016/S0065-2911(08)60134-4 - DOI - PubMed
    1. Smith JL. The Physiological Role of Ferritin-Like Compounds in Bacteria. Crit Rev Microbiol (2004) 30:173–85. doi: 10.1080/10408410490435151 - DOI - PubMed
    1. Almiron M, Link AJ, Furlong D, Kolter R. A Novel DNA-Binding Protein With Regulatory and Protective Roles in Starved Escherichia Coli. Genes Dev (1992) 6:2646–54. doi: 10.1101/gad.6.12b.2646 - DOI - PubMed
    1. Martinez A, Kolter R. Protection of DNA During Oxidative Stress by the Nonspecific DNA-Binding Protein Dps. J Bacteriol (1997) 179:5188–94. doi: 10.1128/jb.179.16.5188-5194.1997 - DOI - PMC - PubMed
    1. Davis MM, Brock AM, DeHart TG, Boribong BP, Lee K, McClune ME, et al. . The Peptidoglycan-Associated Protein NapA Plays an Important Role in the Envelope Integrity and in the Pathogenesis of the Lyme Disease Spirochete. PloS Pathog (2021) 17:e1009546. doi: 10.1371/journal.ppat.1009546 - DOI - PMC - PubMed

Substances