Deciphering rhinovirus-mediated macrophages impairment through the establishment of human induced pluripotent stem cells-derived macrophages

A growing body of evidence suggest that viruses can modulate myeloid cells responses leading to long term impairment of monocytes/macrophages phenotypes.

Whereas for virus directly infecting macrophages, the long-term effects on these cells function and phenotype have been extensively studied, for virus infecting other cell types, the effects on macrophages have been overlooked.

Yet, recent data suggest that virus-mediated modulation of macrophages can even occurred when the virus do not replicate in these cells. Indeed, viruses have broader ways to modulate the innate immune responses than the one identified in permissive cells.

Understanding the mechanisms of action employed by viruses to modulate macrophages responses could not only provide possible targets to eliminate the infection, but also offer therapeutic options to prevent/avoid virus-associated pathogenesis.Human rhinovirus (HRV) impairs macrophages’ responses upon secondary challenge with bacteria.

The host laboratory identified arpin as a critical factor targeted by HRV to alter the phagocytic activity of macrophages and showed that HRV16-treated macrophages present a “paralysed” phenotype in terms of cytokine secretion. The precise mechanisms governing the reprogramming of the macrophages are however not fully elucidated.

Furthermore, it is still unclear whether HRV needs to replicate within macrophages to reprogram their phenotype and functions.

Therefore, my objectives are to decipher (i) if HRV can replicate in alveolar macrophages and (ii) what are the HRV-mediated mechanisms leading to impaired macrophages’ functions.Moreover, the models employed to study macrophages present advantages but do not recapitulate organ physiology, which plays a key role on the resident macrophage phenotype.

Therefore, I will develop a model of human lung alveolar macrophage-like cell (LAML) derived from induced pluripotent stem cells (h-iPSC) to answer the above-mentioned objectives.