Table 1.
Consequences of the treatment of infectious diseases with the FFAR2 ligand acetate.
| Infection model | Targeted cells/organs/effect | Treatment | Outcome | |
|---|---|---|---|---|
| (Antunes et al., 2019) | Pulmonary infection. WT and FFAR2−/− mice infected with respiratory syncytial virus (RSV) | Activation of murine pulmonary epithelial cells via FFAR2 promoted antiviral effects through an IFN-β response. |
Four-week high fiber diet prior and during RSV infection. Or SCFA- drinking water (200 mM) for 3 weeks prior RSV infection |
Acetate treatment protects against RSV infection. |
| (Bautista, 2002) | Gut infection of mice with Clostridium difficile | FFAR2 signaling in neutrophils and in ILC3s | Acetate (150 mM) administered in drinking water before infection | Microbiota-derived acetate coordinates action on neutrophils and ILC3s in response to C. difficile |
| (Galvao et al., 2018) | Pulmonary infection. WT and FFAR2-/- mice infected with Klebsiella pneumoniae | FFAR2 expression, especially in neutrophils and alveolar macrophages, is important for bacterial phagocytosis and killing. | Acetate (150 mM) added to the drinking water of mice | Acetate treatment leads to reduced bacterial numbers in the airways |
| (Sencio et al., 2020) | Pulmonary infection. Infection with influenza A virus and S. pneumoniae superinfection. | Reduced production of acetate affects the bactericidal activity of alveolar macrophages. | Acetate (200 mM) added to the drinking water five days before the S. pneumoniae challenge. | FFAR2 activation during influenza reduces bacterial superinfection |
| (Todorovic et al., 1994) | Gut infection. WT, FFAR3-/- and FFAR2-/- mice infected with Citrobacter rodentium | Acetate administration accelerated IL6, CXCL1/2 expression in epithelia cells and neutrophil/Th17 recruitment in the large cecum | Acetate (200 mM) added to the drinking water for 4 weeks | Acetate-fed WT mice suffered less than untreated mice from infection |
| (Todorovic et al., 1999) | Gut infection. WT and FFAR2-/- mice infected with Citrobacter rodentium | Upon acetate treatment, numbers of colonic IL-22 producing intraepithelial lymphocytes are increased. | Fed with high acetate diet ad libitum for 3 weeks prior and during infection | High SCFA‐producing diets affected infection in mice: less pathogens and altered gut microbiota composition |
| (Corberand et al., 1989) | Gut infection Citrobacter rodentium infection of WT and FFAR2−/− mice | Acetate and butyrate promote B-cell IgG production and plasma cell differentiation-related genes through interaction with FFAR2 on dendritic cells. | Oral immunization with Ovalbumin and cholera toxin. A mixture of acetate/butyrate (300 mM) was added to drinking water containing antibiotics for 28 d. | SCFA administration promoted intestinal antibody responses in WT mice |
| (Laharrague et al., 1985) | Bacteremia, peritonitis Staphylococcus aureus infection of WT and FFAR2−/− mice | Acetate primed neutrophils in a FFAR2-dependent fashion, leading to enhanced neutrophil oxidative burst and bacterial killing. | i.p. injection of 500 mg/kg acetate prior (30 min) or post (6 h) sepsis induction or addition of (150 mM) acetate to drinking water for 5 days. | In WT mice, acetate administration reduced bacterial numbers in peripheral organs by several magnitudes |
SCFAs, Short-chain fatty acids; RSV, respiratory syncytial virus; WT, wild-type; OVA, ovalbumin; ILC3s, type 3 innate lymphoid cells; i.p., intraperitoneal.