DETROIT — The National Institute of Allergy and Infectious Diseases of the National Institutes of Health has awarded a new, five-year $2.4 million R01 grant to Dr. Jiahui Ding, assistant professor of obstetrics and gynecology at the Wayne State University School of Medicine’s C.S. Mott Center for Human Growth and Development, to support research that aims to uncover how viral infections during pregnancy reprogram the developing immune system of the fetus, influencing susceptibility to infectious diseases throughout life.

Maternal viral infections during pregnancy have been associated with adverse pregnancy outcomes and long-term consequences for offspring health. However, scientists do not fully understand how an infection in the mother can alter fetal immune development, particularly when the fetus itself is not directly infected. The project, “Placental Responses to Maternal Viral Infection Drive Sex-Dimorphic Offspring Immune Reprogramming,” focuses on the placenta as a key mediator of that communication.

“This project addresses one of the most important unanswered questions in developmental immunology: how experiences before birth influence immune health across the lifespan,” Ding said. “By understanding how maternal viral infections reprogram fetal immune development, we hope to identify new biomarkers and therapeutic strategies that can reduce susceptibility to infections and improve health outcomes for future generations.”

The findings are expected to provide fundamental insights into why males and females differ in their responses to infections, vaccines and inflammatory diseases following prenatal viral exposure. Ultimately, the research may pave the way for precision medicine approaches that consider fetal sex when developing preventive and therapeutic interventions in pregnancy.

During pregnancy, the placenta acts as an important immune organ that helps educate and shape the developing fetal immune system. When a pregnant mother has an infection, the placenta senses the infection and activates immune responses.

“In this project, we will investigate how the placenta responds to maternal viral infection, how those signals affect developing fetal immune cells, and why these effects can be different between males and females. Ultimately, we hope to better understand how infections during pregnancy can influence immune health later in life and identify potential ways to protect fetal development,” said Ding.

Preliminary findings from Ding’s laboratory indicate that maternal viral infection impairs neutrophil function and increases inflammatory sensitivity predominantly in male offspring, suggesting that placental inflammatory pathways operate in a sex-specific manner during fetal development.

The project will examine how placental inflammasome activation, particularly IL-1β signaling, reshapes fetal hematopoietic stem cells development and establishes long-lasting immune memory. Using cutting-edge approaches, including single-cell transcriptomics, epigenetic profiling and an innovative human placenta–fetal interface organ-on-chip model, the research team will define the molecular pathways linking maternal infection to lifelong immune function.

“I am extremely grateful and excited to receive this award, particularly given the highly competitive funding environment. This support provides an important opportunity for my laboratory to develop a long-term research program focused on how the maternal environment during pregnancy shapes immune development and health in the offspring,” Ding said.

The grant is her first R01 as a principal investigator.

The award represents another major milestone in the Mott Center’s mission to understand the developmental origins of health and disease through collaborative, multidisciplinary research.

“Congratulations to Dr. Jiahui Ding on earning her first NIH R01 award, an outstanding milestone for a promising early-career investigator,” said School of Medicine Dean Dr. Wael Sakr. “This remarkable achievement reflects both her exceptional scientific talent and the collaborative research environment at the C.S. Mott Center. Dr. Ding’s innovative research has the potential to transform our understanding of how maternal health shapes lifelong immune function and to advance precision medicine for future generations. We are proud of her success and look forward to the important discoveries that will emerge from this outstanding work.”

Ding’s earlier work, including studies of Zika virus infection during pregnancy, found that the placenta responds differently depending on fetal sex and that these placental responses are associated with long-lasting and sex-dimorphic differences in offspring neutrophil function.

“Dr. Ding’s NIH R01 exemplifies the scientific vision of the Mott Center, where investigators from diverse disciplines work together to understand how events during pregnancy shape lifelong health,” said Dr. Gil Mor, the John M. Malone Jr. M.D., Endowed Chair of Women’s Health, scientific director of the C.S. Mott Center and vice chair for research in the Department of Obstetrics and Gynecology.

“This project complements several ongoing research programs at the center investigating how maternal infections and environmental exposures influence fetal development and the origins of disease. A defining strength of our research environment is the integration of expertise in reproductive immunology, developmental biology, stem cell biology and systems immunology to uncover the biological basis of sexual dimorphism in disease susceptibility,” Mor said. “Understanding why males and females respond differently to prenatal challenges is central to developing the next generation of precision medicine strategies for mothers and children.”

The C.S. Mott Center for Human Growth and Development at Wayne State University is a nationally recognized multidisciplinary research center dedicated to advancing discoveries in reproductive biology, pregnancy, fetal development, cancer, environmental health and the developmental origins of disease. Through collaborative basic, translational and clinical research, the center seeks to improve the health of women, children and families while training the next generation of biomedical scientists.

“Dr. Ding’s research has the potential to prevent lifelong health challenges in children who have been exposed to infections before birth,” said Dr. Ezemenari Obasi, vice president for research & innovation at Wayne State University. “I look forward to the impact this research will have in our community and beyond.”

Research cited in this article was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number R01AI201310. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Learn more about Ding’s research and lab at https://wayne.edu/people/gy3378.

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Wayne State University is one of the nation’s pre-eminent public research universities in an urban setting. Through its multidisciplinary approach to research and education, and its ongoing collaboration with government, industry and other institutions, the university seeks to enhance economic growth and improve the quality of life in the city of Detroit, state of Michigan and throughout the world. For more information about research at Wayne State University, visit research.wayne.edu.

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The intricate landscape of the upper airway microbiota serves not simply as a passive reservoir but as an active participant in modulating pathogen colonization and persistence. Researchers Kelly, Shi, Boiditswe, and colleagues have systematically investigated how this microbial community interacts with respiratory viruses and bacterial pathobionts during this formative period in infancy, an age marked by rapid immunological and physiological changes. This study, recently published in Nature Communications, dissects the temporal shifts and interspecies dynamics that underpin respiratory infection risks in the most vulnerable demographic.

Central to the study’s significance is the recognition that the first 12 months of life represent an immunological crucible, during which the infant’s respiratory tract is frequently challenged by viral infections ranging from common cold viruses to more severe pathogens. Concurrently, bacterial species with pathobiont potential—microbes capable of tipping the scales toward disease under certain circumstances—take residence. The research delves into how these bacterial populations shift and interact in response to viral incursions and how such microbial interactions influence disease trajectories.

Using longitudinal sampling and state-of-the-art metagenomic sequencing techniques, the investigators charted the developmental trajectory of the upper airway microbiota in a large cohort of infants. They achieved a granular view of how viral infections, such as those caused by respiratory syncytial virus (RSV) or rhinoviruses, perturb the microbial equilibrium. The findings reveal that viral episodes often precede significant alterations in bacterial composition, highlighting a bidirectional relationship with important clinical ramifications.

One of the study’s indispensable revelations is the temporal coupling between respiratory viruses and particular bacterial taxa, notably species within the genera Streptococcus and Moraxella. The data demonstrate that viral infections can enhance the colonization and proliferation of these bacteria, increasing the risk of secondary bacterial infections, which are a common and sometimes severe complication in infants. This observation underscores the microbiota’s role not simply as a bystander but as a mediator of disease exacerbation.

Moreover, the research sheds light on the mechanistic underpinnings of these interactions. Viral infection-induced inflammation creates a microenvironment conducive to bacterial overgrowth and shifts in immune signaling pathways. Such changes impair mucosal barrier function and modulate local immune responses, thus promoting bacterial persistence and potentially contributing to sustained or recurrent infections. These insights deepen our understanding of the pathophysiology of respiratory illnesses and open avenues for targeted therapeutic strategies.

The interdependence of host immunity, viral pathogens, and bacterial communities featured prominently throughout the investigation. Infants with particular microbiota profiles demonstrated distinct responses to viral infections, suggesting that early microbial composition may predict susceptibility or resilience. This raises compelling questions regarding whether interventions that modulate the microbiota could enhance protection or mitigate severity during critical stages of immune system development.

Attention was also devoted to the concept of microbial succession over the pivotal first year, a time when the infant’s immune system is not fully matured. The study documented a shift from a relatively simple microbial community toward more complex and potentially pathogenic configurations, which may prime the respiratory tract for either health or disease. Understanding the drivers of these ecological shifts is crucial for designing preventive and therapeutic approaches that capitalize on microbiome modulation.

Given the study’s extensive and meticulous methodology, the use of high-throughput sequencing technologies allowed for the characterization of viral-bacterial interactions at an unprecedented resolution. This technological innovation provided data not only on presence and abundance but also on functional capacities of the microbial communities, highlighting metabolic pathways and virulence factors potentially involved in respiratory disease pathogenesis.

The researchers emphasize the implications of their findings in the context of vaccine development and antimicrobial stewardship. Recognizing the microbiota’s role in respiratory infection dynamics encourages a paradigm shift from solely targeting pathogens to considering the broader microbial ecosystem. Strategies that maintain or restore beneficial microbial balance could complement existing interventions, reducing the burden of respiratory disease in infants.

Furthermore, this research offers a compelling model for understanding chronic respiratory conditions with roots in early life, such as asthma and recurrent wheezing. Disruptions in the early airway microbiota may set the stage for immune dysregulation and heightened inflammatory responses later in life. Thus, the insights gleaned from this study extend beyond infectious disease to chronic respiratory health.

The interplay between the microbiota and viral pathogens also has evolutionary implications. Microbial ecosystems that coexist with the host can influence virus transmission dynamics and evolutionary trajectories, potentially affecting virus virulence and pathogenicity. Understanding these relationships could inform public health strategies during viral epidemics, especially in pediatric populations.

Importantly, the study’s longitudinal design overcomes limitations of cross-sectional analyses by capturing dynamic processes as they unfold. This temporal perspective reveals patterns of microbial resilience, vulnerability, and adaptability, painting a comprehensive picture of infant upper airway ecology that static snapshots cannot provide.

While the findings mark a significant advance, the authors acknowledge the need for further research to translate these observations into clinical practice. Unraveling the causal mechanisms behind observed correlations and identifying specific microbial functions that confer protection or risk remain critical tasks. Additionally, individual genetic factors and environmental influences must be integrated to form a holistic understanding.

In conclusion, the work by Kelly and colleagues illuminates the complex, intertwined relationships between the upper airway microbiota, respiratory viruses, and bacterial pathobionts during infancy. Their research not only enhances our understanding of microbial ecology and immunology at a crucial developmental stage but also sets the stage for innovative interventions aimed at safeguarding respiratory health from the very beginning of life.

Subject of Research: The role of the upper airway microbiota in modulating respiratory virus and bacterial pathobiont dynamics during the first year of life in infants.

Article Title: Role of the upper airway microbiota in respiratory virus and bacterial pathobiont dynamics in the first year of life.

Article References:
Kelly, M.S., Shi, P., Boiditswe, S.C. et al. Role of the upper airway microbiota in respiratory virus and bacterial pathobiont dynamics in the first year of life.
Nat Commun 16, 5195 (2025). https://doi.org/10.1038/s41467-025-60552-4

Image Credits: AI Generated