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Microbes & Immunity Role of SRCR proteins in inflammation

immune response to pathogens but also confer significant Consent for publication
anti-inflammatory effects that contribute to homeostasis
within the immune system. CD5L, in particular, Not applicable.
underscores the complementary roles of these proteins, Availability of data
demonstrating pronounced anti-inflammatory activities
that complement their microbial recognition capabilities. Not applicable.
Furthermore, the contributions of cell-surface molecules References
such as CD5, CD6, CD163, and CD163L1 highlight the 1. Martínez VG, Moestrup SK, Holmskov U, Mollenhauer J,
complexity of the SRCR family, especially within the Lozano F. The conserved scavenger receptor cysteine-rich
contexts of infection and inflammation. While these superfamily in therapy and diagnosis. Pharmacol Rev.
surface proteins may display limited microbial recognition 2011;63(4):967-1000.
capabilities due to their location on cell membranes, their
proteolytic cleavage during inflammatory or infectious doi: 10.1124/pr.111.004523
conditions generates soluble forms, which can exert critical 2. Martínez VG, Escoda-Ferran C, Tadeu Simões I, et al. The
regulatory influences on inflammation and immune macrophage soluble receptor AIM/Api6/CD5L displays a
responses. broad pathogen recognition spectrum and is involved in
early response to microbial aggression. Cell Mol Immunol.
Overall, the interplay between soluble and membrane- 2014;11(4):343-354.
bound SRCR proteins highlights their therapeutic doi: 10.1038/cmi.2014.12
potential in addressing inflammatory disorders and
infectious diseases. Future research focused on elucidating 3. Miró-Julià C, Roselló S, Martínez VG, et al. Molecular and
the detailed mechanisms governing these proteins functional characterization of mouse S5D-SRCRB: A new
will pave the way for innovative therapeutic strategies, group B member of the scavenger receptor cysteine-rich
superfamily. J Immunol. 2011;186(4):2344-2354.
enhancing our ability to modulate immune responses and
improve host defense against pathogens effectively. As doi: 10.4049/jimmunol.1000840
our understanding deepens, SRCR proteins may become 4. Bessa Pereira C, Bockova M, Santos RF, et al. The scavenger
essential targets for developing cutting-edge treatments receptor SSc5D physically interacts with bacteria through
that exploit their multifaceted roles in immune regulation. the SRCR-containing N-terminal domain. article. Front
Immunol. 2016;7:416.
Acknowledgments
doi: 10.3389/fimmu.2016.00416
None. 5. Cardoso MS, Santos RF, Almeida S, et al. Physical
interactions with bacteria and protozoan parasites establish
Funding the scavenger receptor SSC4D as a broad-spectrum pattern
This work was supported by National Funds through recognition receptor. Front Immunol. 2021;12:760770.
Fundação para a Ciência e a Tecnologia (FCT), I.P., under doi: 10.3389/fimmu.2021.760770
the projects 2022.04792.PTDC and European Society of 6. Alharbi AF, Sheng N, Nicol K, Stromberg N, Hollox EJ.
Clinical Microbiology and Infectious Diseases (ESCMID) Balancing selection at the human salivary agglutinin gene
Individual Research Grant to L.O. (DMBT1) driven by host-microbe interactions. iScience.
2022;25(5):104189.
Conflict of interest
doi: 10.1016/j.isci.2022.104189
The authors declare they have no conflict of interest.
7. Reichhardt MP, Meri S. SALSA: A regulator of the early
Author contributions steps of complement activation on mucosal surfaces. Front
Immunol. 2016;7:85.
Conceptualization: Liliana Oliveira, Alexandre M. Carmo doi: 10.3389/fimmu.2016.00085
Visualization: Maria Carolina Silva, Liliana Oliveira
Writing – original draft: Maria Carolina Silva, Rita P. Pinto 8. Muller H, Nagel C, Weiss C, Mollenhauer J, Poeschl J.
Writing – review & editing: Liliana Oliveira, Alexandre M. Deleted in malignant brain tumors 1 (DMBT1) elicits
Carmo increased VEGF and decreased IL-6 production in type II
lung epithelial cells. BMC Pulm Med. 2015;15:32.
Ethics approval and consent to participate doi: 10.1186/s12890-015-0027-x
Not applicable. 9. Renner M, Bergmann G, Krebs I, et al. DMBT1 confers

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