Mammalian senescent nurse cell provides Trichinella spp. muscle larvae with cell growth inhibitory capacity

Muscle larva of the mammalian parasitic nematode Trichinella spp. resides in a single cell called a nurse cell (NC). Despite originating from muscle cells the NC is of the non-muscular type. Its only role is to sustain muscle larva throughout the host's life. Our previous studies documented cellular senescence as the main phenomenon associated with the NC development and its long-term maintenance. Cell-cycle arrest of the NC was underpinned by p57 Kip2 cyclin-dependent kinase inhibitor (CDKI) expression. Since p16 INK4a and p21 Cip1 CDKIs are recommended as the key markers of growth arrest in in situ senescence examination their expression and localization in the NC-larva complexes were followed in the current study. A model of murine trichinellosis was employed. CDKN2a gene encoding p16 INK4a and CDKN1a gene encoding p21 Cip1 were upregulated in the mature NC at 7-month old infection. However, only p16 INK4a was upregulated on the protein level during the NC development at 26-day old infection, as well as in the mature NC at 7-month old infection. Both CDKIs localized to the larva at two time points of infection. It is hypothesized that Trichinella muscle larvae may absorb mammalian CDKIs while encysted in the NCs. These CDKIs may exert growth-inhibitory role in the parasite and/or if transferred to the offspring they may participate in the establishment of new NCs in the next host. These hypotheses await functional validation.