How does the gut microbiota influence infection? One of the important papers on this area was published in 1979 by MacDonald and Carter, in which the authors showed that germfree mice did not mount a delayed-type hypersensitivity (DTH) response after being sensitized with sheep red blood cells. Several papers had already shown a dichotomy between antibody and cellular immune responses (Parish and Liew 1972). Research led in several labs with Leishmania major led to the Th1/Th2 paradigm (Sacks and Noben-Trauth 2002). The paper by MacDonald and Carter suggested to us that maybe germfree mice would respond to L. major with a Th2 response, since they were unable to mount a DTH response, a bona fide Th1 response that leads to resistance to the parasite. Since the early 1990s, our lab has been trying to understand the relationship between the intestinal microbiota and parasitic diseases, such as leishmaniasis and Chaga’s disease in experimental models. Much to our surprise, our findings have determined that mice mount similar Th responses to Leishmania major and to Trypanosoma cruzi (Oliveira et al. 2005). The most remarking finding is that germfree mice are more susceptible to infection with L. major and that seems to be because their macrophages, which host Leishmania, are less likely to be activated to an inflammatory phenotype. Rather, they are more capable of sustaining the growth of L. major. Hence, the microbiota seems to have the effect of “training” macrophages for the inflammatory phenotype, leading to resistance to the parasite (Lopes et al. 2021). These studies are ongoing, and it seems that there will be more surprising effects of our commensals in health and disease.
Funding
LQV is funded by CNPq grant numbers 304588/2013–0, 309789/2017–5, and 400729/2014–8, in part by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, (CAPES) Finance Code 001 and FAPEMIG grant number CBB APQ-01993–12 (Brazil).
Declarations
Conflict of interest
The author declares no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
- Lopes ME, dos Santos LM, Sacks D, Vieira LQ, Carneiro MB (2021) Resistance against Leishmania major infection depends on microbiota-guided macrophage activation. Front Immunol 12:730437. 10.3389/fimmu.2021.730437 [DOI] [PMC free article] [PubMed]
- MacDonald TT, Carter PB. Requirement for a Bacterial Flora before Mice Generate Cells Capable of Mediating the Delayed Hypersensitivity Reaction to Sheep Red Blood Cells. J Immunol. 1979;122:2624. [PubMed] [Google Scholar]
- Oliveira MR, Tafuri WL, Afonso LC, Oliveira MA, Nicoli JR, Vieira EC, Scott P, Melo MN, Vieira LQ (2005) Germ-free mice produce high levels of interferon-gamma in response to infection with Leishmania Major but fail to heal lesions. Parasitology 131:477. 10.1017/S0031182005008073 [DOI] [PubMed]
- Sacks D, Noben-Trauth N (2002) The immunology of susceptibility and resistance to Leishmania Major in Mice. Nat Rev Immunol 2:845. 10.1038/nri933 [DOI] [PubMed]
- Parish CR, Liew, FY (1972) Immune response to chemically modified flagelin. 3. enhanced Cell-mediated immunity during high and low zone antibody tolerande to flagellin. J Exp Med 2:298. 10.1084/jem.135.2.298 [DOI] [PMC free article] [PubMed]