Modeling Host-Pathogen Interaction Using Lymphoid Organoids

Background:

Staphylococcus aureus (S. aureus) are bacteria that can make people sick. Sometimes, an S. aureus infection can develop inside the spine; these infections can lead to paralysis and death. Researchers do not know how S. aureus interacts with a person s cells to cause infections in the spine.

Objective:

To learn how S. aureus interacts with cells in the body using tissues from tonsils discarded after standard surgery to remove them.

Eligibility:

People aged 2 years and older who are scheduled to have their tonsils removed.

Design:

Researchers will select participants for the study based on review of their existing medical records, including results of blood tests; any imaging scans, including x-rays; and reports about tissue specimens.

Participants will answer questionnaires about their health and past infections. They can do this online or on paper.

Participants will collect a nasal swab 1 week before their surgery. They will be given a tool that looks like a long cotton swab. They will twirl it around inside their nose. The swab will pick up cells and fluids that will be used for research.

After their surgery, the participant s surgeon will save samples of tonsil tissue. The surgeon will send these tissue samples and the nasal swab to researchers at the NIH.

These tissues and the swab will be used in studies to help researchers understand how S. aureus interacts with cells in the body. They hope these studies will help them find better ways to treat S. aureus infections.

STUDY DESCRIPTION:

The purpose of this study is to collect tonsil tissues that are routinely discarded after tonsillectomy procedures to develop lymphoid organoid models to evaluate host-pathogen interactions in human health and disease. One such interaction is the human immunotolerance mechanism to the Chemotaxis Inhibitory Protein of S. aureus (CHIPS).

OBJECTIVES:

Primary Objectives:

-Develop a lymphoid organoid model from discarded human tonsils and determine and compare the human immunologic signatures of primary exposure, within the antigenic sin contexts of re-exposure, and with repeated exposures to CHIPS.

Secondary Objective:

-Modulate anti-CHIPS IgG4 class switching through variation of primary and costimulatory signals.

ENDPOINTS:

Primary Endpoints:

Differences between the following within the antigenic sin contexts of re-exposure, and with repeated exposures to CHIPS:

* Immune cell composition.
* Anti-CHIPS antibody levels, including total and subclasses of IgG and their neutralizing capacity.
* Cytokine levels.
* Activation-induced cytidine deaminase (AID) levels.
* Single-cell inference of class switch recombination (sciCSR).

Secondary Endpoints:

Differences between the following modulation of primary and costimulatory signals:

* Immune cell composition.
* Anti-CHIPS antibody levels, including total and subclasses of IgG and their neutralizing capacity.
* Cytokine levels.
* AID levels.
* sciCSR

Eligibility Criteria:
* INCLUSION CRITERIA:

To be eligible to participate in this study, an individual must meet all of the following criteria:

* Aged \>=2 years.
* Undergoing tonsillectomy as part of their clinical care.
* Able to provide informed consent (for ages \>=18 years) or has a parent or guardian who can provide informed consent on their behalf (for ages \<18 years).
* Willing to allow samples and data to be stored and shared for future secondary research.
* Willing to allow future genetic testing on their biospecimens.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

* Active infection.
* Active tonsilitis.
* Pregnant.
* Diagnosed with an immunosuppressive condition or currently taking immunosuppressive medications.
* Current or past intravenous drug use.
* Any condition that, in the judgment of the investigator, may put the participant at undue risk or make them unsuitable for participation in the study