Infantile pneumonia (IP) is an inflammation of the lungs caused by pathogens (such as bacteria and viruses) and other factors (such as inhalation of amniotic fluid and meconium). It is the most common respiratory disease in infants and young children [1]. According to WHO data, IP accounted for 14 % of all deaths in children under 5 years of age and caused 740,180 deaths in children under the age of 5 in 2019. Moreover, pneumonia in severe cases can result in cardiovascular disease and other complications [2,3]. Currently, antiviral and antibacterial treatments remain the main methods for IP treatment; however, pathogen resistance is increasing with the overuse of antibiotics, which makes it difficult to cure [4]. Thus, it is necessary to further understand the pathogenesis of IP and discover more effective targets for IP therapy.

Flawed epigenetic patterns are a common characteristic of numerous human diseases, and growing evidence suggests a significant role for epigenetic therapy related to gene therapy in personalized precision medicine [5]. Epigenetic modifications strongly affect cellular regulation and function. RNA epigenetics is a prominent field of epitranscriptomics [6]. N6-Methyladenosine (m6A) is the most abundant RNA methylation modification in mammalian cells, and it is involved in many biological processes, including cell differentiation, death, self-renewal, and invasion, affecting mRNA stability, splicing, and translation [7,8]. The m6A modification is initiated by m6A methyltransferases, and its function is executed by m6A-binding proteins directly or indirectly [9,10]. METTL3 is the catalytic subunit of the methyltransferase complex that catalyzes the methylation of its specific target transcripts [11], and has been implicated in both pathological and physiological processes [10,12]. Li et al. showed that METTL3 deficiency could reduce m6A levels in severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2), thereby increasing RIG-I binding and subsequent sensing and activation of innate immune responses [13]. Moreover, METTL3 promoted SARS-CoV-2 viral replication [14]. METTL3 stabilizes NEAT1 expression via m6A modification and enhances its binding with CTCF to promote MUC19 transcription, thereby facilitating Streptococcus pneumoniae-evoked inflammation and apoptosis in alveolar epithelial cells (AECs) [15]. In addition, METTL3 was found to be increased in patients with IP, and silencing of METTL3 suppressed lipopolysaccharide (LPS)-stimulated apoptotic and inflammatory injuries in cell models (WI-38) of pediatric pneumonia via EZH2 [16]. However, the precise function and mechanism of action of METTL3 in IP remain unclear.

In the present study, we used LPS to establish IP cells and mouse models to investigate the role of METTL3 in IP-induced lung injury. In addition, mRNAs that could be methylated by METTL3 were explored to clarify the role of METTL3 in IP progression. This study identified a new target for IP prevention.