# CRISPR-Cas9 Screening and Simulated Infection Transcriptomic Identify Key Drivers of Innate Immunity in Bactrian Camels

## TL;DR

This study uses gene editing and gene expression analysis to uncover how Bactrian camels fight infections, revealing key genes involved in their immune system.

## Contribution

The study provides the first systematic mapping of the innate immune landscape in Bactrian camels using CRISPR-Cas9 and transcriptomics.

## Key findings

- CRISPR screening identified 59 key genes important for immune defense against pathogens.
- Antiviral and antibacterial responses rely on distinct genetic mechanisms.
- HSP90AA1 and CSF1 were identified as pivotal genes in antiviral and antibacterial processes, respectively.

## Abstract

Bactrian camels are animals known for surviving in harsh environments, with unique physiological and immune adaptations. This study aimed to understand how they defend against viral and bacterial infections. By combining gene-editing technology with gene expression analysis, the researchers systematically identified key genes important for fighting viruses and bacteria. The results showed that the genetic mechanisms of antiviral and antibacterial activity are not entirely the same. Key genes such as HSP90AA1 and CSF1 were found to play central roles in immune defense. These findings improve our understanding of camel immunology and provide new insights into how mammals adapt immune systems to infections. In the future, this knowledge could help breed more disease-resistant livestock and support sustainable animal farming.

The Bactrian camel (Camelus bactrianus), with its unique physiological adaptations and immune characteristics, represents a highly valuable model for innate immunity research. However, a systematic dissection of its innate immune gene repertoire and the key functional drivers within its immune response remains limited. This study integrated CRISPR-Cas9 knockout screening with time-resolved transcriptomic profiling to systematically unveil the immune regulatory mechanisms in camel dermal fibroblasts challenged with the viral mimic poly(I:C) and the bacterial mimic LPS. The CRISPR screen successfully identified 59 key genes conferring a survival advantage under lethal pathogenic challenge. The gene sets required for resisting viral versus bacterial mimics were entirely distinct, revealing divergent genetic underpinnings. Transcriptomic analysis further delineated a dynamic reprogramming of gene expression, uncovering a shared core immune response program alongside significant stimulus-specific regulation. Integrative analysis pinpointed pivotal genes, such as HSP90AA1 in the antiviral process and CSF1 in the antibacterial process, which played critical roles at both the functional screening and transcriptional regulatory levels. These key genes exhibited dynamic and evolving co-expression networks across different time points, indicating their temporally specific regulatory roles throughout the immune response. By combining functional genomics and transcriptomics, this study provides the first systematic mapping of the innate immune landscape and its dynamic regulation in the Bactrian camel, not only deepening the understanding of camelid immunobiology but also offering a new framework and insights for evolutionary studies of immune adaptation mechanisms in mammals.