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A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection
Published on: February 28, 2019
Dietary Bovine Lactoferrin Reduces Staphylococcus aureus in the Tissues and Modulates the Immune Response in Piglets
Elizabeth A Reznikov1, Sarah S Comstock2, Jennifer L Hoeflinger3
1Division of Nutritional Sciences.
Insights
Bovine lactoferrin (bLf) reduced Staphylococcus aureus infection severity in piglets, showing benefits alone or with Bifidobacterium infantis. However, B. infantis alone did not improve outcomes and may hinder immune response during S. aureus infection.
Area of Science:
- Immunology
- Microbiology
- Neonatal Health
Background:
- Bovine lactoferrin (bLf) is known to combat Staphylococcus aureus infections and promote beneficial gut bacteria in infants.
- The combination of bLf and Bifidobacterium infantis was hypothesized to reduce systemic S. aureus infection severity.
Purpose of the Study:
- To evaluate the impact of oral bLf and B. infantis on the progression of systemic S. aureus infection in a piglet model.
- To understand the immune responses and bacterial load changes associated with bLf and B. infantis administration.
Main Methods:
- Colostrum-deprived piglets were fed either a control formula (CON), bLf (LF), B. infantis (BI), or a combination (COMB).
- After infection with S. aureus, immune markers, bacterial counts in tissues, and gene expression were analyzed.
Main Results:
- Dietary bLf improved piglet weight gain and reduced S. aureus counts in kidneys, lungs, and heart.
- bLf modulated immune responses, including decreased kidney IL-10 and increased lung IFN-γ mRNA, while B. infantis alone increased splenic IFN-γ and serum IL-10.
- Combined administration showed some benefits, but B. infantis alone was associated with decreased memory T cells and increased IL-10 post-infection.
Conclusions:
- Bovine lactoferrin demonstrates efficacy against S. aureus infection, with independent and tissue-specific effects.
- While bLf supports an effective immune response, B. infantis administration during S. aureus infection is not supported by this study.
- Findings provide biological rationale for bLf's clinical benefits in preterm infants.
Background:
Bovine lactoferrin (bLf) reduces Staphylococcus aureus infection in premature infants and promotes the growth of Bifidobacterium infantis, a predominant infant gut species. We hypothesized that bLf in combination with B. infantis would reduce the severity of systemic S. aureus infection.
Objective:
The aim was to determine the effects of oral administration of bLf and B. infantis on the course of systemic S. aureus infection.
Methods:
Colostrum-deprived piglets were fed formulas containing 4 g whey/L (CON group) or bLf (LF group). One-half of the piglets in each group were gavaged with B. infantis (109 colony-forming units/d), resulting in 2 additional groups (BI or COMB, respectively). On day 7, piglets were intravenously injected with S. aureus. Blood samples were collected preinfection and every 12 h postinfection for immune analyses. Tissue samples were collected on day 12 for analysis of bacterial abundance and gene expression.
Results:
Preinfection, LF piglets had lower serum interleukin 10 (IL-10), a higher percentage of lymphocytes, and a lower percentage of neutrophils than BI or COMB piglets. After infection, dietary bLf increased piglet weight gain, reduced staphylococcal counts in the kidneys, and tended to lower staphylococcal counts in the lungs and heart. Dietary bLf also decreased kidney IL-10 and increased lung interferon γ (IFN-γ) mRNA. B. infantis increased splenic IFN-γ expression. Renal Toll-like receptor 2 was upregulated in BI piglets but not in COMB piglets. Postinfection, BI piglets had increased serum IL-10 and decreased memory T cell populations. LF and COMB piglets had fewer circulating monocytes and B cells than CON or BI piglets.
Conclusions:
Dietary bLf and B. infantis produced independent and tissue-specific effects. Piglets fed bLf alone or in combination with B. infantis mounted a more effective immune response and exhibited lower bacterial abundance. This study provides biological underpinnings to the clinical benefits of bLf observed in preterm infants but does not support B. infantis administration during S. aureus infection.
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