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Cell-mediated immunity to intestinal infection
Abstract:
Specified pathogen-free B6D2F1 mice were orally infected with various doses of Listeria monocytogenes. Oral inocula containing more than 2.5 X 10(8) live organisms consistently initiated infection in the Peyer's patches (PP) of the small intestine. At lower doses the infection was sporadic, with many mice showing no apparent infection in the PP. The PP appeared to be the only site of tissue invasion and L. monocytogenes survival in the intestinal tissues, as no organisms were recovered from mucosa dissected free of all visible PP. Within the PP, the bacteria multiplied and the infection then disseminated to the mesenteric lymph node (MLN), liver, and spleen. However, bacteria were almost completely eliminated from all tissues, both systemic and gut-associated by 6 days postinfection. Mice given a primary L. monocytogenes infection by the oral route were highly resistant to subsequent intravenous or oral challenge. Likewise, sublethal intravenous infection rendered mice highly resistant to subsequent oral infection. In addition, lymphocytes from the PP, MLN, and spleens of mice recovering from a primary oral infection were able to adoptively transfer immunity to normal recipients. Finally, after oral infection, mice did not display peripheral delayed hypersensitivity to L. monocytogenes antigens until the organisms had penetrated to the spleen.
Insights
Oral infection with Listeria monocytogenes primarily targets Peyer's Patches (PP) in mice, leading to systemic immunity. This study demonstrates oral infection establishes resistance against subsequent Listeria challenges.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Listeria monocytogenes is a foodborne pathogen that can cause serious infections.
- The gastrointestinal tract is a potential route of infection for L. monocytogenes.
- Understanding the initial sites of infection and immune response is crucial for developing effective countermeasures.
Purpose of the Study:
- To investigate the initial site of Listeria monocytogenes invasion following oral infection in mice.
- To characterize the dissemination and clearance of L. monocytogenes after oral inoculation.
- To determine the development of protective immunity after oral L. monocytogenes infection.
Main Methods:
- Specified pathogen-free B6D2F1 mice were orally infected with varying doses of Listeria monocytogenes.
- Infection sites and bacterial load were assessed in Peyer's Patches (PP), mesenteric lymph nodes (MLN), liver, and spleen.
- Immunity was evaluated through subsequent challenge infections (oral and intravenous).
- Adoptive transfer of lymphocytes was used to assess the transfer of immunity.
Main Results:
- Oral inoculation with >2.5 X 10^8 L. monocytogenes consistently infected Peyer's Patches (PP).
- PP served as the primary site for invasion and survival, with subsequent dissemination to MLN, liver, and spleen.
- L. monocytogenes was cleared from all tissues by 6 days post-infection.
- Prior oral or intravenous infection conferred significant resistance to subsequent challenges.
- Immunity could be adoptively transferred via lymphocytes from infected and recovering mice.
Conclusions:
- Peyer's Patches are the primary intestinal site for Listeria monocytogenes invasion and initial replication following oral infection.
- Oral Listeria monocytogenes infection induces a robust and transferable immune response conferring protection against subsequent infections.
- The study highlights the importance of the gut-associated lymphoid tissue in initiating protective immunity against systemic pathogens.