Leishmania (V.) braziliensis infection promotes macrophage autophagy by a LC3B-dependent and BECLIN1-independent mechanism

• Published in: Acta tropica 2021-06, Vol.218, p.105890-105890, Article 105890
• Main Authors: Duque, Thabata Lopes Alberto, Serrão, Thamires Christinne de Souza Lopes Cruz, Gonçalves, Antônio José da Silva, Pinto, Eduardo Fonseca, Oliveira-Neto, Manoel Paes, Pirmez, Claude, Pereira, Luiza de Oliveira Ramos, Menna-Barreto, Rubem Figueiredo Sadok
• Format: Article
• Language: English
• Subjects: Autophagy; BECLIN1; LC3B; Leishmania spp; Leishmaniasis; Macrophages
• ISSN: 0001-706X; 1873-6254
• DOI: 10.1016/j.actatropica.2021.105890

•In early infection, THP-1 macrophages cultured with Leishmania braziliensis delayed LC3 mobilization.•During late infection, the percentage of LC3+ cells increased in infected culture.•Autophagy induction, through rapamycin treatment or starvation, reduced infection at 24h.•Autophagy downregulation by LC3B but not BECLIN1 siRNA increased infection. Leishmania (Viannia) braziliensis is one of the main etiological agents of tegumentary leishmaniasis in Latin America. The establishment of a successful infection in host cells requires several key events including phagocytosis, phagolysosomal maturation impairment, and parasite replication. Autophagy is accountable for the physiological turnover of cellular organelles, degradation of macromolecular structures, and pathogen elimination. In many cases, autophagy control leads to a successful infection, both impairing pathogen elimination or providing nutrients. Here, we have investigated the relationship between autophagy and L. braziliensis infection. We observed that BECLIN1 expression was upregulated early on infection in both in vitro macrophage cultures and biopsies of cutaneous lesions from L. braziliensis infected patients. On the other hand, LC3B expression was downregulated in cutaneous lesions biopsies. A transient pattern of LC3+ cells was observed along L. braziliensis infection, but the number of LC3 puncta did not vary. Additionally, autophagy induction, with rapamycin treatment or through starvation, reduced infection. As expected, rapamycin increased the percentage of LC3+ cells and the number of puncta, but the presence of parasite restricted this effect, indicating LC3-associated autophagy impairment by L. braziliensis. Finally, silencing LC3B but not BECLIN1 promoted infection, confirming BECLIN1 independent and LC3B-related control by the parasite. Taken together, these data indicate macrophage autophagic machinery manipulation by L. braziliensis, resulting in successful establishment and survival into the host cell. [Display omitted]