# Functions and Mechanisms of Lung Microfold cells during Invasive Pneumococcal Disease

> **NIH NIH K99** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $171,450

## Abstract

PROJECT SUMMARY
 Bacterial coinfections have been the leading cause of severe illness and mortality during past
Influenza pandemics and current seasonal endemics. Streptococcus pneumoniae is the most common
etiological agent reported during Influenza-associated secondary infections. Unfortunately, the epithelial and
immunological mechanisms resulting in increased pneumococcal invasion, persistence, and dissemination
in the Influenza aftermath remain poorly understood. Preliminary data suggest that Microfold (M) cells arise
in the lung epithelium during the resolution phase of Influenza-associated inflammation when susceptibility
to pneumococcal infections is maximum. Highly endocytic intestinal M cells play a crucial role in gut immune
surveillance by directly delivering luminally captured antigens to underlying dendritic cells, eliciting antigen-
specific mucosal immunity. However, M cells in the gut are occasionally hijacked and serve as entry portals
for pathogenic dissemination into the host. Having been only recently identified, our knowledge of lung M cell
functions in pulmonary infection and immunity is scant. Our single-cell transcriptomic analysis of the murine
airway epithelium reveals M cell-specific expression of novel transcytosis receptors, chemokines, and
regulators of endocytic trafficking with immunomodulatory properties. This proposal aims to define the
functional role of lung M cells in predisposition to influenza-associated pneumococcal invasion and ensuing
pneumonia and sepsis. We further aim to identify the intracellular trafficking mechanisms during
pneumococcal transcytosis across airway M cells. The proposed research goals will be achieved by
employing in vitro and in vivo models of M cell induction in the lower airways coupled with genetically
engineered mouse models for M cell ablation and innovative live imaging platforms. This study will shed light
on the M cell-driven mechanisms promoting invasive pneumococcal disease and will inform the development
of ingenious therapeutic strategies to target epithelial entry portals, thus preventing bacterial superinfections
in the background of viral infections. The proposed research plan will be executed at the MGH Center for
Regenerative Medicine (CRM), Boston, under the mentorship of Dr. Jayaraj Rajagopal, an expert in the field
of airway epithelial biology and lung regeneration. My career objective is to become a tenure-track faculty
pioneering and simultaneously training next-generation scientists in the field of lung infections and immunity.
To accomplish my career goals, I have put together a comprehensive training plan to enhance the overall
skill sets required to establish myself as a successful independent investigator. To ensure timely progress
toward fulfilling my rigorous research plan and career goals, I have gathered an expert advisory committee
comprising Dr. Dennis Brown, Dr. Jatin Vyas, and Dr. David Scadden, with whom I will regularly discuss my
research progre...

## Key facts

- **NIH application ID:** 10984196
- **Project number:** 1K99HL171884-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Manalee V Surve
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $171,450
- **Award type:** 1
- **Project period:** 2024-09-01 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10984196

## Citation

> US National Institutes of Health, RePORTER application 10984196, Functions and Mechanisms of Lung Microfold cells during Invasive Pneumococcal Disease (1K99HL171884-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10984196. Licensed CC0.

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