bims-nocaut 2024-03-10 papers

Nat Cell Biol. 2024 Mar 04.

Retraction Note: Molecular characterization of LC3-associated phagocytosis reveals distinct roles for Rubicon, NOX2 and autophagy proteins.

Jennifer Martinez, R K Subbarao Malireddi, Qun Lu, Larissa Dias Cunha, Stephane Pelletier, Sebastien Gingras, Robert Orchard, Jun-Lin Guan, Haiyan Tan, Junmin Peng, Thirumala-Devi Kanneganti, Herbert W Virgin, Douglas R Green.

DOI: https://doi.org/10.1038/s41556-024-01383-1

J Exp Med. 2024 Apr 01. pii: e20230774. [Epub ahead of print]221(4):

NADPH oxidase exerts a B cell-intrinsic contribution to lupus risk by modulating endosomal TLR signals.

Shuozhi Liu, Jonathan Lagos, Natali M Shumlak, Andrea D Largent, Sebastien T E Lewis, Ursula Holder, Samuel W Du, Yifan Liu, Baidong Hou, Mridu Acharya, Shaun W Jackson.

Genome-wide association studies in systemic lupus erythematosus (SLE) have linked loss-of-function mutations in phagocytic NADPH oxidase complex (NOX2) genes, including NCF1 and NCF2, to disease pathogenesis. The prevailing model holds that reduced NOX2 activity promotes SLE via defective efferocytosis, the immunologically silent clearance of apoptotic cells. Here, we describe a parallel B cell-intrinsic mechanism contributing to breaks in tolerance. In keeping with an important role for B cell Toll-like receptor (TLR) pathways in lupus pathogenesis, NOX2-deficient B cells exhibit enhanced signaling downstream of endosomal TLRs, increased humoral responses to nucleic acid-containing antigens, and the propensity toward humoral autoimmunity. Mechanistically, TLR-dependent NOX2 activation promotes LC3-mediated maturation of TLR-containing endosomes, resulting in signal termination. CRISPR-mediated disruption of NCF1 confirmed a direct role for NOX2 in regulating endosomal TLR signaling in primary human B cells. Together, these data highlight a new B cell-specific mechanism contributing to autoimmune risk in NCF1 and NCF2 variant carriers.

DOI: https://doi.org/10.1084/jem.20230774

Microbiol Mol Biol Rev. 2024 Mar 07. e0005222

Interplay between group A Streptococcus and host innate immune responses.

Marcia Shu-Wei Su, Yi-Lin Cheng, Yee-Shin Lin, Jiunn-Jong Wu.

SUMMARYGroup A Streptococcus (GAS), also known as Streptococcus pyogenes, is a clinically well-adapted human pathogen that harbors rich virulence determinants contributing to a broad spectrum of diseases. GAS is capable of invading epithelial, endothelial, and professional phagocytic cells while evading host innate immune responses, including phagocytosis, selective autophagy, light chain 3-associated phagocytosis, and inflammation. However, without a more complete understanding of the different ways invasive GAS infections develop, it is difficult to appreciate how GAS survives and multiplies in host cells that have interactive immune networks. This review article attempts to provide an overview of the behaviors and mechanisms that allow pathogenic GAS to invade cells, along with the strategies that host cells practice to constrain GAS infection. We highlight the counteractions taken by GAS to apply virulence factors such as streptolysin O, nicotinamide-adenine dinucleotidase, and streptococcal pyrogenic exotoxin B as a hindrance to host innate immune responses.

Keywords: LC3-associated phagocytosis; autophagy; complement system; group A Streptococcus; inflammation; innate immunity; phagocytosis; pyroptosis

DOI: https://doi.org/10.1128/mmbr.00052-22