Mast cells and histamine alter intestinal permeability during malaria parasite infection

Area of Science:

• Immunology
• Infectious Diseases
• Gastroenterology

Background:

• Co-infections with malaria and non-typhoidal Salmonella serotypes (NTS) can lead to severe bacteremia.
• Previous studies linked malaria/NTS co-infection to gut mast cell activation, histamine release, increased gut permeability, and bacterial translocation.

Purpose of the Study:

• To investigate the role of mast cells and histamine in malaria-associated gut pathology and bacterial translocation.
• To determine if mast cell activation and histamine release occur during falciparum malaria alone.

Main Methods:

• Utilized mouse models of malaria and malaria/NTS co-infection.
• Assessed gut mastocytosis, plasma histamine levels, gut permeability, and bacterial translocation.
• Compared outcomes in mast cell-deficient mice and wild-type mice.
• Administered antihistamine treatment to evaluate its effect on pathology.

Main Results:

• Gut mastocytosis and elevated plasma histamine were observed in both malaria/NTS co-infection and falciparum malaria models.
• Mast cell-deficient mice exhibited reduced gut permeability and bacteremia during malaria/NTS co-infection.
• Antihistamine treatment decreased bacterial translocation and gut permeability in mice with malaria.

Conclusions:

• Mast cell-derived histamine contributes to gastrointestinal pathology and increased bacteremia risk during malaria/NTS co-infection.
• Targeting mast cell activation or histamine may be a therapeutic strategy for managing malaria co-infections.