# Synergistic effects of silica exposure, virus infection and genetic predisposition in systemic autoimmunity

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 2020 · $399,375

## Abstract

Project Summary 
 
Systemic lupus erythematosus (SLE), the prototypic systemic autoimmune disease, is characterized by 
immune system hyperactivation, autoantibody production, and multiorgan inflammation. Although genetic 
predisposition is critical for disease expression, the low concordance rate in monozygotic twins (<40%) 
suggests the essential contribution of additional factors, mostly provided through environmental exposures. 
Indeed, significant epidemiological evidence has linked SLE and other systemic autoimmune disease to 
crystalline silica exposure but also to certain viral infections. Considering the critical role of innate immune 
activation in systemic autoimmunity, we hypothesized that silica inhalation, virus infection, and genetic 
predisposing factors synergize by activating distinct innate immunostimulatory pathways, that together lead to 
more efficient break of tolerance, earlier disease onset, and more severe autoimmune manifestations. In 
support of this hypothesis, we provide preliminary evidence that silica and virus exposures more effectively 
induce autoimmune manifestations in mouse models of lupus when given in combination than when given 
individually. Here we will use this experimental system to define the mechanistic basis of the interplay 
between virus infection and silica, including the temporal requirements of silica exposure and virus infection, 
the contribution of innate inflammatory pathways differentially induced by silica and virus, and roles of these 
factors in breaking immunological tolerance.

## Key facts

- **NIH application ID:** 10053262
- **Project number:** 1R01ES031082-01A1
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** ROBERTO G BACCALA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $399,375
- **Award type:** 1
- **Project period:** 2020-07-01 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10053262

## Citation

> US National Institutes of Health, RePORTER application 10053262, Synergistic effects of silica exposure, virus infection and genetic predisposition in systemic autoimmunity (1R01ES031082-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10053262. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*