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<p>Using a horse foal model, we show that enteral immunization of newborn foals with <i>Rhodococcus equi</i> overcomes neonatal vaccination challenges by reprogramming innate immune responses, inducing <i>R. equi</i>-specific adaptive humoral and cell-mediated immune responses and protecting foals against experimental pneumonia challenge. Foals were immunized twice via gavage of <i>R. equi</i> (immunized group) or saline (control group) at ages 1 and 3 days. At age 28 days, all foals were challenged intrabronchially with <i>R. equi</i>. Post-challenge, all 5 immunized foals remained healthy, whereas 67% (4/6) of control foals developed clinical pneumonia. Immunized foals exhibit changes in the epigenetic profile of blood monocytes, &gt; 1,000 differentially-expressed genes in neutrophils, higher concentrations of <i>R. equi</i>-specific IgG<sub>1</sub> and IgG<sub>4/7</sub>, and a higher number of IFN-γ producing lymphocytes in response to <i>R. equi</i> stimulation indicating T helper type 1 response compared to control foals. Together, our data indicate that early life exposure to <i>R. equi</i> in the gastrointestinal tract can modulate innate immune responses, generate specific antibodies and cell-mediated immunity, and protect against pneumonia.</p>

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Enteral immunization with live bacteria reprograms innate immune cells and protects neonatal foals from pneumonia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月25日

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  • Bibiana Petri da Silveira,
  • Susanne K. Kahn,
  • Rebecca M. Legere,
  • Jocelyne M. Bray,
  • Hannah M. Cole-Pfeiffer,
  • Michael C. Golding,
  • Noah D. Cohen,
  • Angela I. Bordin

摘要

Using a horse foal model, we show that enteral immunization of newborn foals with Rhodococcus equi overcomes neonatal vaccination challenges by reprogramming innate immune responses, inducing R. equi-specific adaptive humoral and cell-mediated immune responses and protecting foals against experimental pneumonia challenge. Foals were immunized twice via gavage of R. equi (immunized group) or saline (control group) at ages 1 and 3 days. At age 28 days, all foals were challenged intrabronchially with R. equi. Post-challenge, all 5 immunized foals remained healthy, whereas 67% (4/6) of control foals developed clinical pneumonia. Immunized foals exhibit changes in the epigenetic profile of blood monocytes, > 1,000 differentially-expressed genes in neutrophils, higher concentrations of R. equi-specific IgG1 and IgG4/7, and a higher number of IFN-γ producing lymphocytes in response to R. equi stimulation indicating T helper type 1 response compared to control foals. Together, our data indicate that early life exposure to R. equi in the gastrointestinal tract can modulate innate immune responses, generate specific antibodies and cell-mediated immunity, and protect against pneumonia.