黑料网

Brain mast cells; Neuroimmunology; CNS infections; Bacterial infections; Viral infections; Immune modulation; Therapeutic targets

Introduction

Mast cells are tissue-resident immune cells primarily known for their roles in allergic reactions and inflammation. Traditionally studied in peripheral tissues, recent research has identified mast cells within the brain, termed brain mast cells (BMCs). BMCs are strategically positioned within the blood-brain barrier (BBB) and the meninges, suggesting they play crucial roles in neuroinflammation and neuroimmune responses [1]. While BMCs' roles in neurodegenerative diseases and neuroinflammatory conditions have been explored, their potential in responding to bacterial and viral infections in the brain remains an area of active investigation. BMCs are equipped with receptors for various pathogens and immune mediators, allowing them to sense and respond to infectious agents within the CNS [2]. Upon activation, BMCs release a spectrum of cytokines, chemokines, and other immune modulators that can shape local immune responses. This capacity is critical for initiating and regulating neuroinflammation in response to infections [3]. Studies suggest that BMCs play a dual role in both promoting immune defense and contributing to pathological processes in CNS infections, depending on the context and the specific pathogen involved [4]. In bacterial infections such as meningitis or encephalitis, BMCs are activated by bacterial components or cytokines released by infected cells [5]. Activation triggers BMCs to release pro-inflammatory cytokines like TNF-α, IL-6, and IL-1β, which recruit and activate microglia and other immune cells to clear the infection. Additionally, BMCs can release antimicrobial peptides and proteases that directly target pathogens, enhancing the local immune response [6]. In viral infections, BMCs respond to viral particles and nucleic acids, contributing to antiviral immunity through interferon production and activation of adaptive immune responses within the CNS. Harnessing BMCs' immunomodulatory capabilities holds promise for developing novel therapeutic strategies against CNS infections [7]. Approaches could include enhancing BMC activation to bolster immune responses in cases of immunodeficiency or dampening BMC activation to mitigate neuroinflammation and tissue damage in conditions like viral encephalitis or autoimmune disorders affecting the CNS [8]. Targeted modulation of BMC responses could also be explored to improve outcomes in bacterial meningitis or neuroinvasive viral infections where traditional treatments have limitations.

Challenges and future directions

Despite their potential, several challenges exist in harnessing BMCs for therapeutic use. These include understanding the precise roles of BMCs in different CNS infections, optimizing methods for targeting BMCs without compromising BBB integrity, and ensuring safety in manipulating neuroimmune responses. Future research should focus on elucidating BMCs' specific contributions to CNS immunity, exploring novel delivery methods for BMC-targeted therapies, and conducting preclinical and clinical trials to evaluate the efficacy and safety of BMC-based treatments in infectious diseases affecting the brain [9-12].

Conclusion

Brain mast cells represent a novel frontier in neuroimmunology, offering unique opportunities for therapeutic intervention in bacterial and viral infections of the CNS. Their ability to sense pathogens, modulate local immune responses, and interact with neural cells underscores their potential as therapeutic targets. Further research into BMC biology and their precise roles in infection control is essential for realizing the therapeutic promise of these intriguing immune cells.

Acknowledgement

None

Conflict of Interest

None

References

1. Sehgal IS, Dhooria S, Agarwal R (2017) . Curr Opin Pulm Med 23: 139-148.

, ,

2. Vestbo J, Hurd SS, Agustí AG, Jones PW, Vogelmeier C, et al. (2013) . Am J Respir Crit Care Med 187: 347–365.

, ,

3. Choudhury G, Rabinovich R, MacNee W (2014) . Clin Chest Med 35: 101-130.

, ,

4. Itoh M, Tsuji T, Nemoto K, Nakamura H, Nakamura H, et al. (2013) . Nutrients 5:  1316–1335.

, ,

5. Girón R, Matesanz C, García-Río F, Santiago ED, Mancha A, et al. (2009) . Ann Nutr Metab 54: 52-58.

, ,

6. Gupta B, Kant S, Mishra R, Verma S (2010) . J Clin Med Res 2: 68-74.

, ,

7. Hoong JM, Ferguson M, Hukins C, Collins PF (2017) . Clin Nutr 36: 1105–1109.

, ,

8. Hallin R, Gudmundsson G, Ulrik CS, Nieminen MM, Gislason T, et al. (2007) . Respir Med 101: 1954-1960.

, ,

9. Ukleja A, Gilbert K, Mogensen KM, Walker R, Ward CT, et al. (2018) . Nutr Clin Pract 33: 906–920.

, ,

10. Ferguson M, Capra S, Bauer J, Banks M (1999) . Nutrition 15: 458–464.

, ,

11. Kruizenga HM, Seidell JC, De-Vet HCW, Wierdsma NJ, van Bokhorst-de van der Schueren MAE (2005)  . Clin Nutr 24: 75–82.

, ,

12. Stratton RJ, Hackston A, Longmore D, Dixon R, Price S, et al. (2004) . Br J Nutr 92: 799–808.

, ,