Langerhans cells

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Section of skin showing large numbers of dendritic cells (Langerhans cells) in the epidermis. (M. ulcerans infection, S100 immunoperoxidase stain.)
The representation of Langerhans cells in the Cell Ontology. A portion of the Cell Ontology is shown with ovals corresponding to cell types defined in the ontology and arrows corresponding to relations between those cell types. Langerhans cell is represented by a yellow oval; blue arrows correspond to is_a relations, and orange arrows correspond to develops_from relations. Only a subset of Langerhans cell parent types are included in the figure.[1]

Langerhans cells are dendritic cells (antigen-presenting immune cells) of the skin and mucosa, and contain large granules called Birbeck granules. They are present in all layers of the epidermis, but are most prominent in the stratum spinosum.[2] They also occur in the papillary dermis, particularly around blood vessels,[2] as well as in the oral mucosa, foreskin, and vagina.[3] They can be found in other tissues, such as lymph nodes, particularly in association with the condition Langerhans cell histiocytosis (LCH).

History

The Langerhans cell is named after Paul Langerhans, a German physician and anatomist, who discovered the cells at the age of 21 while he was a medical student.[4] Because of their dendritic nature, he mistakenly identified the cells as part of the nervous system.[5]

Function

In skin infections, the local Langerhans cells take up and process microbial antigens to become fully functional antigen-presenting cells.

Generally, dendritic cells in biological tissue are active in the capture, uptake and processing of antigens. Once dendritic cells arrive in secondary lymphoid tissue, however, they lose these properties while gaining the capacity to interact with naive T-cells.

Langerhans cells derive from the cellular differentiation of monocytes with the marker "Gr-1" (also known as "Ly-6G/Ly-6C"). This differentiation requires stimulation by colony stimulating factor (CSF)-1.[6] They are similar in morphology and function to macrophages.

Langerin is a protein found in Langerhans cells,[7] and other types of dendritic cells.[8]

Clinical significance

LCH

In the rare disease Langerhans cell histiocytosis (LCH), an excess of these cells is produced. This can cause damage to skin, bone and other organs.

HIV

Former hypothesis

Kawamura et al. (2005) suggested Langerhans cells may be initial cellular targets in the sexual transmission of HIV,[9] and as a target, reservoir, and vector of dissemination.[10]

Hussain & Lehner (2005) observed Langerhans cells have been observed in foreskin, vaginal, and oral mucosa of humans; the lower concentrations in oral mucosa suggest that it is not a likely source of HIV infection relative to foreskin and vaginal mucosa.[3]

Present view

On 4 March 2007 the online Nature Medicine magazine published the letter "Langerin is a natural barrier to HIV-1 transmission by Langerhans cells."[11] One of the authors of the study, Teunis Geijtenbeek, said that "Langerin is able to scavenge viruses from the surrounding environment, thereby preventing infection" and "since generally all tissues on the outside of our bodies have Langerhans cells, we think that the human body is equipped with an antiviral defense mechanism, destroying incoming viruses."[12]

Population-based studies

September 2021 saw the publication of two huge population studies on the relationship of circumcision and HIV infection:

  1. Mayan et al. (2021) carried out a massive empirical study of the male population of the province of Ontario, Canada (569,950 males), of whom 203,588 (35.7%) were circumcised between 1991 and 2017. The study concluded that circumcision status is not related to risk of HIV infection.[13]
  2. Morten Frisch & Jacob Simonsen (2021) carried out a large scale empirical population study in Denmark of 855,654 males regarding the alleged value of male circumcision in preventing HIV and other sexually transmitted infections in men. They found that circumcised men have a higher rate of STI and HIV infection overall than intact men.[14]

No association between lack of circumcision and risk of HIV infection was found by either study. There now is credible evidence that the massive, expensive African circumcision programs have not been effective in preventing HIV infection.

Two African surveys

The previously reported studies were from developed Western nations. Now we have information from Sub_Saharan Africa.

French scientist Michel Garenne, Ph.D. has published two reports in 2022 comparing the incidence of HIV infection in circumcised and intact men.

In his first report, Garenne presented the findings from a study in Lesotho, the enclave in South Africa. He reported:

In couple studies, the effect of circumcision and VMMC on HIV was not significant, with similar transmission from female to male and male to female. The study questions the amount of effort and money spent on VMMC in Lesotho.[15]

In his second report, Garenne (2022) presented information from six Sub-Saharan African nations (Eswatini, Lesotho, Malawi, Namibia, Zambia, Zimbabwe). He reported:

"Results matched earlier observations made in South Africa that circumcised and intact men had similar levels of HIV infection."[16]

See also

References

  1. ↑ REFjournal Masci A, Arighi CN, Diehl AD, Lieberman AE, Mungall C, Scheuermann RH, Smith B, Cowell LG. An improved ontological representation of dendritic cells as a paradigm for all cell types. BMC Bioinformatics. 2009; 10(70) PMID. PMC. DOI. Retrieved 20 October 2019.
  2. ↑ a b REFbook Young B, Heath JW (2000): Wheater's Functional Histology. Edition: 4. Churchill Livingstone. P. 162. ISBN 0-443-05612-9.
  3. ↑ a b REFjournal Hussain LA, Lehner T. Comparative investigation of Langerhans' cells and potential receptors for HIV in oral, genitourinary and rectal epithelia. Immunology. July 1995; 85(3): 475-484. PMID. PMC. Retrieved 20 October 2019.
  4. ↑ REFjournal Langerhans P. Über die Nerven der menschlichen Haut [On the nerves of the human skin] (German). Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin. 1868; 44(2-3): 325-337. DOI. Retrieved 20 October 2010.
  5. ↑ REFweb McKusick, Victor A (20 April 2000). Langerhans cell histiocytosis, OMIM. Retrieved 20 October 2019.
  6. ↑ REFjournal Ginhoux F, Tacke F, Angeli V, Bogunovic M, Loubeau M, Dai XM, Stanley ER, Randolph GJ, Merad M. Langerhans cells arise from monocytes in vivo. Nature Immunology. 26 January 2016; 7(3): 265-273. PMID. DOI. Retrieved 20 October 2019.
  7. ↑ REFjournal Valladeau J, Dezutter-Dambuyant C, Saeland S. Langerin/CD207 Sheds Light on Formation of Birbeck Granules and Their Possible Function in Langerhans Cells. Immunologic Research. October 2003; 28(2): 93-107. PMID. DOI. Retrieved 20 October 2010.
  8. ↑ REFjournal Poulin LF, Henri S, de Bovis B, Devilard E, Kissenpfennig A, Malissen B. The dermis contains langerin+ dendritic cells that develop and function independently of epidermal Langerhans cells. Journal of Experimental Medicine. 24 December 2007; 204(13): 3119-3131. PMID. PMC. DOI. Retrieved 20 October 2019.
  9. ↑ REFjournal Kawamura T, Kurtz SE, Blauvelt A, Shimada S. The role of Langerhans cells in the sexual transmission of HIV. Journal of Dermatological Science. December 2005; 40(3): 147-155. PMID. DOI.
  10. ↑ REFjournal Dezutter-Dambuyant C, Charbonnier AS, Schmitt D. Cellules dendritiques épithéliales et infection par HIV-1 in vivo et in vitro [Epithelial dendritic cells and HIV-1 infection in vivo and in vitro] (French). Pathologie Biologie. December 1995; 43(10): 882-888. PMID. Retrieved 20 October 2019.
  11. ↑ REFjournal de Witte L, Nabatov A, Pion M, Fluitsma D, de Jong MAWP, de Gruijl T, Piguet V, van Kooyk Y, Geijtenbeek TBH. Langerin is a natural barrier to HIV-1 transmission by Langerhans cells PDF. Nature Medicine. 4 March 2007; 13(3): 367-71. PMID. PMC. DOI. Retrieved 6 October 2022.
  12. ↑ REFnews Mundell, E. J. (5 March 2007)."Scientists Discover 'Natural Barrier' to HIV", HealthDay, MSN. Retrieved 27 June 2012.
  13. ↑ REFjournal Mayan M, Hamilton RJ, Juurlink DN, Austin PC, Jarvi KA. Circumcision and Risk of HIV Among Males From Ontario, Canada. J Urol. 23 September 2021; PMID. DOI. Retrieved 21 August 2022.
    Quote: We found that circumcision was not independently associated with the risk of acquiring HIV among men from Ontario, Canada.
  14. ↑ REFjournal Frisch M, Simonsen J. Non-therapeutic male circumcision in infancy or childhood and risk of human immunodeficiency virus and other sexually transmitted infections: national cohort study in Denmark. Eur J Epidemiol. 26 September 2021; 37: 251–9. PMID. DOI. Retrieved 16 January 2022.
  15. ↑ REFjournal Garenne M. Changing relationships between HIV prevalence and circumcision in Lesotho. J Biosoc Sci. 4 April 2022; online ahead of print: 1-16. PMID. DOI. Retrieved 28 October 2022.
  16. ↑ REFjournal Garenne M. Age-incidence and prevalence of HIV among intact and circumcised men: an analysis of PHIA surveys in Southern Africa. J Biosoc Sci. 26 October 2022; : 1-13. PMID. DOI. Retrieved 27 October 2022.
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