The human microbiota, a diverse community of microorganisms living on or within their hosts, play an irreplaceable role in maintaining human health. Dysbiosis of the microbiota is associated with the pathogenesis of diverse human diseases. In recent years, growing evidence has been presented to support the substantial effect of human microbiota on the progression of infectious diseases. In this review, we describe the functional role of human microbiota in infectious diseases by highlighting their Janus-faced effects in the regulation of acute and chronic infections as well as their related co-morbidities. Thereafter, we review the latest advances elucidating the mechanisms underlying tri-directional interactions between the microbiota, hosts, and invading pathogens, with a further discussion on external environmental factors that shape this interconnected regulatory network. A better understanding of the regulatory functions and mechanisms of human microbiota in infectious diseases will facilitate the development of new diagnostic, preventive, and therapeutic approaches for infectious diseases.

The local immune defenses of respiratory system play a crucial role in safeguarding against pathogens and eliminating infected cells. In this article, we review the current knowledge regarding the establishment and regulation of local immune responses within the lungs, with a particular focus on the formation of inducible bronchus-associated lymphoid tissue (iBALT), which has demonstrated a capacity to mount protective immune responses against several pathogens, including influenza virus, severe acute respiratory syndrome coronavirus (SARS-CoV)/SARS-CoV-2, and Mycobacterium tuberculosis (Mtb). Furthermore, we explore the development and regulation of long-term immune memory within the lungs, which may be facilitated by iBALT. This review aims to provide a summary of potential targets within iBALT for pathogen defense and vaccine design.