Close Encounters of Lymphoid Cells and Bacteria

Abstract

During infections, the first reaction of the host against microbial pathogens is carried out by innate immune cells, which recognize conserved structures on pathogens, called pathogen-associated molecular patterns. Afterward, some of these innate cells can phagocytose and destroy the pathogens, secreting cytokines that would modulate the immune response to the challenge. This rapid response is normally followed by the adaptive immunity, more specific and essential for a complete pathogen clearance in many cases. Some innate immune cells, usually named antigen-presenting cells, such as macrophages or dendritic cells, are able to process internalized invaders and present their antigens to lymphocytes, triggering the adaptive immune response. Nevertheless, the traditional boundary of separated roles between innate and adaptive immunity has been blurred by several studies, showing that very specialized populations of lymphocytes (cells of the adaptive immunity) behave similarly to cells of the innate immunity. These “innate-like” lymphocytes include γδ T cells, invariant NKT cells, B-1 cells, mucosal-associated invariant T cells, marginal zone B cells, and innate response activator cells, and together with the newly described innate lymphoid cells are able to rapidly respond to bacterial infections. Strikingly, our recent data suggest that conventional CD4+ T cells, the paradigm of cells of the adaptive immunity, also present innate-like behavior, capturing bacteria in a process called transinfection. Transinfected CD4+ T cells digest internalized bacteria like professional phagocytes and secrete large amounts of proinflammatory cytokines, protecting for further bacterial challenges. In the present review, we will focus on the data showing such innate-like behavior of lymphocytes following bacteria encounter.

Building conventions for unconventional lymphocytes

“…PRRs, however, are found on an array of different cell types, not just specialized innate immune cells. For non-immune cells such as epithelial cells(6), neurons(7), and even conventional adaptive immune cells(8), PPR expression establishes intracellular innate immune protective pathways that allow these cells to inform specialized immune cells of a potential infection.…”

“…NKT cells were originally defined as NK cell marker NK1.1 + αβT cells with invariant TCRs (thus “NK like” T cells). However, over time their definition has become both broader and more specific to be MHC-I non-classical molecule CD1d-responsive αβT cells that are also positive for some NK-cell markers, though not necessarily NK1.1 (as some mouse strains do not express NK1.1)(8). CD1d is the molecule of its type expressed in mice, though humans have several CD1 types including CD1a, b, c, and d(25).…”

“…These include unconventional T cells restricted to other non-classical MHC-I molecules, including H2-M3, Qa1 and HFE(36), as well as unconventional B cells such as B-1 cells(8) and marginal zone (MZ) B cells(37). There is also a heterogeneously complex population of cells called intraepithelial lymphocytes (IELs) that have unconventional lymphocyte behavior and include members of unconventional lymphocyte populations described above as well as other cell types.…”

“…However, over time their definition has become both broader and more specific to be MHC-I non-classical molecule CD1d-responsive αβT cells that are also positive for some NK-cell markers, though not necessarily NK1.1 (as some mouse strains do not express NK1.1). 8 CD1d is the molecule of its type expressed in mice, though humans have several CD1 types including CD1a, b, c, and d. 25 Invariant NKT cells (iNKTs or Type I NKTs) commonly express the TCR Vα14-Jα18 and either Vβ8, Vβ7 or Vβ2 in mice, or Vα24-Jα18 and Vβ11 in humans. 25 In addition to iNKTs, there are also NKT cells that respond to CD1d but are less restricted in their TCR repertoire and do not share the canonical TCR of iNKTs.…”

“…These in-between cells are often classified as 'innate-like' because they display some of the key aspects of innate immune cells: (i) they exhibit quick kinetics with immediate effector functions that, unlike adaptive cells, do not require a maturation phase, and (ii) they carry PRRs, respond to PRR stimulation, and, according to some reports in the literature, can play the role of APCs. 8,38 However, these are classical functions of innate immune cells found in every tissue where unconventional lymphocytes can also be found. Why are these cells maintained if they are redundant with innate immune cells?…”