Role of myeloid cells expressing CD169/Siglec-1 in host-pathogen interactions

CD169/Siglec-1 is a type-I transmembrane lectin receptor expressed on subcapsular sinus macrophages and activated monocytes, which plays a key role in innate immune surveillance and orchestration of adaptive immunity. As a sialic acid-binding immunoglobulin-like lectin (Siglec), CD169 recognizes sialylated gangliosides and glycoconjugates present on surface of several viral envelopes, including HIV-1, SARS-CoV-2, and Ebola virus as well as sialylated bacterial capsules such as those of Neisseria meningitidis and Campylobacter jejuni. Moreover, different viruses were shown to be captured by CD169+ cells which could play distinctive role during infections: they could enhance efficient immune responses, but also facilitate pathogen dissemination through viral capture and transfer to permissive cells. This last mechanism has been well documented for HIV-1, where CD169 mediates viral trans-infection of CD4⁺ T-cells. CD169 expression is rapidly induced by type-I interferons during acute viral infections and has emerged as a valuable biomarker to distinguish viral from bacterial infection, particularly for COVID-19 and influenza. Detectable by flow cytometry, CD169 represents a solid biomarker in clinical settings and possible target in the development of novel prophylactic and therapeutic strategies. Its dual role, protective in host defence yet exploitable by certain pathogens, highlights the need for careful consideration in future therapeutic approaches.